research paper based on nanotechnology

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Materials Advances

Nanomaterials: a review of synthesis methods, properties, recent progress, and challenges.

* Corresponding authors

a Center of Research Excellence in Desalination & Water Treatment, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia E-mail: [email protected] , [email protected]

b Center for Environment and Water, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

c Interdisciplinary Research Center for Membranes and Water Security, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

d Department of Chemical & Biological Engineering, University of Alabama, Tuscaloosa, Alabama 35487-0203, USA E-mail: [email protected] , [email protected]

e Department of Mechanical Engineering, King Fahd University of Petroleum and Minerals, Dhahran 31261, Saudi Arabia

Nanomaterials have emerged as an amazing class of materials that consists of a broad spectrum of examples with at least one dimension in the range of 1 to 100 nm. Exceptionally high surface areas can be achieved through the rational design of nanomaterials. Nanomaterials can be produced with outstanding magnetic, electrical, optical, mechanical, and catalytic properties that are substantially different from their bulk counterparts. The nanomaterial properties can be tuned as desired via precisely controlling the size, shape, synthesis conditions, and appropriate functionalization. This review discusses a brief history of nanomaterials and their use throughout history to trigger advances in nanotechnology development. In particular, we describe and define various terms relating to nanomaterials. Various nanomaterial synthesis methods, including top-down and bottom-up approaches, are discussed. The unique features of nanomaterials are highlighted throughout the review. This review describes advances in nanomaterials, specifically fullerenes, carbon nanotubes, graphene, carbon quantum dots, nanodiamonds, carbon nanohorns, nanoporous materials, core–shell nanoparticles, silicene, antimonene, MXenes, 2D MOF nanosheets, boron nitride nanosheets, layered double hydroxides, and metal-based nanomaterials. Finally, we conclude by discussing challenges and future perspectives relating to nanomaterials.

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N. Baig, I. Kammakakam and W. Falath, Mater. Adv. , 2021,  2 , 1821 DOI: 10.1039/D0MA00807A

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Nanotechnology

Purpose-led Publishing is a coalition of three not-for-profit publishers in the field of physical sciences: AIP Publishing, the American Physical Society and IOP Publishing.

Together, as publishers that will always put purpose above profit, we have defined a set of industry standards that underpin high-quality, ethical scholarly communications.

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Nanotechnology encompasses the understanding of the fundamental physics, chemistry, biology and technology of nanometre-scale objects.

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Yi-Teng Huang et al 2021 Nanotechnology 32 132004

Lead-halide perovskites have demonstrated astonishing increases in power conversion efficiency in photovoltaics over the last decade. The most efficient perovskite devices now outperform industry-standard multi-crystalline silicon solar cells, despite the fact that perovskites are typically grown at low temperature using simple solution-based methods. However, the toxicity of lead and its ready solubility in water are concerns for widespread implementation. These challenges, alongside the many successes of the perovskites, have motivated significant efforts across multiple disciplines to find lead-free and stable alternatives which could mimic the ability of the perovskites to achieve high performance with low temperature, facile fabrication methods. This Review discusses the computational and experimental approaches that have been taken to discover lead-free perovskite-inspired materials, and the recent successes and challenges in synthesizing these compounds. The atomistic origins of the extraordinary performance exhibited by lead-halide perovskites in photovoltaic devices is discussed, alongside the key challenges in engineering such high-performance in alternative, next-generation materials. Beyond photovoltaics, this Review discusses the impact perovskite-inspired materials have had in spurring efforts to apply new materials in other optoelectronic applications, namely light-emitting diodes, photocatalysts, radiation detectors, thin film transistors and memristors. Finally, the prospects and key challenges faced by the field in advancing the development of perovskite-inspired materials towards realization in commercial devices is discussed.

Karl Berggren et al 2021 Nanotechnology 32 012002

Recent progress in artificial intelligence is largely attributed to the rapid development of machine learning, especially in the algorithm and neural network models. However, it is the performance of the hardware, in particular the energy efficiency of a computing system that sets the fundamental limit of the capability of machine learning. Data-centric computing requires a revolution in hardware systems, since traditional digital computers based on transistors and the von Neumann architecture were not purposely designed for neuromorphic computing. A hardware platform based on emerging devices and new architecture is the hope for future computing with dramatically improved throughput and energy efficiency. Building such a system, nevertheless, faces a number of challenges, ranging from materials selection, device optimization, circuit fabrication and system integration, to name a few. The aim of this Roadmap is to present a snapshot of emerging hardware technologies that are potentially beneficial for machine learning, providing the Nanotechnology readers with a perspective of challenges and opportunities in this burgeoning field.

Daniele Ielmini and Stefano Ambrogio 2020 Nanotechnology 31 092001

Artificial intelligence (AI) has the ability of revolutionizing our lives and society in a radical way, by enabling machine learning in the industry, business, health, transportation, and many other fields. The ability to recognize objects, faces, and speech, requires, however, exceptional computational power and time, which is conflicting with the current difficulties in transistor scaling due to physical and architectural limitations. As a result, to accelerate the progress of AI, it is necessary to develop materials, devices, and systems that closely mimic the human brain. In this work, we review the current status and challenges on the emerging neuromorphic devices for brain-inspired computing. First, we provide an overview of the memory device technologies which have been proposed for synapse and neuron circuits in neuromorphic systems. Then, we describe the implementation of synaptic learning in the two main types of neural networks, namely the deep neural network and the spiking neural network (SNN). Bio-inspired learning, such as the spike-timing dependent plasticity scheme, is shown to enable unsupervised learning processes which are typical of the human brain. Hardware implementations of SNNs for the recognition of spatial and spatio-temporal patterns are also shown to support the cognitive computation in silico . Finally, we explore the recent advances in reproducing bio-neural processes via device physics, such as insulating-metal transitions, nanoionics drift/diffusion, and magnetization flipping in spintronic devices. By harnessing the device physics in emerging materials, neuromorphic engineering with advanced functionality, higher density and better energy efficiency can be developed.

Syed Nabeel Ahmed and Waseem Haider 2018 Nanotechnology 29 342001

There has been a considerable amount of research in the development of sustainable water treatment techniques capable of improving the quality of water. Unavailability of drinkable water is a crucial issue especially in regions where conventional drinking water treatment systems fail to eradicate aquatic pathogens, toxic metal ions and industrial waste. The research and development in this area have given rise to a new class of processes called advanced oxidation processes, particularly in the form of heterogeneous photocatalysis, which converts photon energy into chemical energy. Advances in nanotechnology have improved the ability to develop and specifically tailor the properties of photocatalytic materials used in this area. This paper discusses many of those photocatalytic nanomaterials, both metal-based and metal-free, which have been studied for water and waste water purification and treatment in recent years. It also discusses the design and performance of the recently studied photocatalytic reactors, along with the recent advancements in the visible-light photocatalysis. Additionally, the effects of the fundamental parameters such as temperature, pH, catalyst-loading and reaction time have also been reviewed. Moreover, different techniques that can increase the photocatalytic efficiency as well as recyclability have been systematically presented, followed by a discussion on the photocatalytic treatment of actual wastewater samples and the future challenges associated with it.

Lior Shani et al 2024 Nanotechnology 35 255302

Semiconductor nanowire (NW) quantum devices offer a promising path for the pursuit and investigation of topologically-protected quantum states, and superconducting and spin-based qubits that can be controlled using electric fields. Theoretical investigations into the impact of disorder on the attainment of dependable topological states in semiconducting nanowires with large spin–orbit coupling and g -factor highlight the critical need for improvements in both growth processes and nanofabrication techniques. In this work, we used a hybrid lithography tool for both the high-resolution thermal scanning probe lithography and high-throughput direct laser writing of quantum devices based on thin InSb nanowires with contact spacing of 200 nm. Electrical characterization demonstrates quasi-ballistic transport. The methodology outlined in this study has the potential to reduce the impact of disorder caused by fabrication processes in quantum devices based on 1D semiconductors.

Achint Jain et al 2018 Nanotechnology 29 265203

Integrating layered two-dimensional (2D) materials into 3D heterostructures offers opportunities for novel material functionalities and applications in electronics and photonics. In order to build the highest quality heterostructures, it is crucial to preserve the cleanliness and morphology of 2D material surfaces that come in contact with polymers such as PDMS during transfer. Here we report that substantial residues and up to ∼0.22% compressive strain can be present in monolayer MoS 2 transferred using PDMS. We show that a UV-ozone pre-cleaning of the PDMS surface before exfoliation significantly reduces organic residues on transferred MoS 2 flakes. An additional 200 ◦ C vacuum anneal after transfer efficiently removes interfacial bubbles and wrinkles as well as accumulated strain, thereby restoring the surface morphology of transferred flakes to their native state. Our recipe is important for building clean heterostructures of 2D materials and increasing the reproducibility and reliability of devices based on them.

Arne Laucht et al 2021 Nanotechnology 32 162003

Quantum phenomena are typically observable at length and time scales smaller than those of our everyday experience, often involving individual particles or excitations. The past few decades have seen a revolution in the ability to structure matter at the nanoscale, and experiments at the single particle level have become commonplace. This has opened wide new avenues for exploring and harnessing quantum mechanical effects in condensed matter. These quantum phenomena, in turn, have the potential to revolutionize the way we communicate, compute and probe the nanoscale world. Here, we review developments in key areas of quantum research in light of the nanotechnologies that enable them, with a view to what the future holds. Materials and devices with nanoscale features are used for quantum metrology and sensing, as building blocks for quantum computing, and as sources and detectors for quantum communication. They enable explorations of quantum behaviour and unconventional states in nano- and opto-mechanical systems, low-dimensional systems, molecular devices, nano-plasmonics, quantum electrodynamics, scanning tunnelling microscopy, and more. This rapidly expanding intersection of nanotechnology and quantum science/technology is mutually beneficial to both fields, laying claim to some of the most exciting scientific leaps of the last decade, with more on the horizon.

U Banin et al 2021 Nanotechnology 32 042003

This roadmap on Nanotechnology for Catalysis and Solar Energy Conversion focuses on the application of nanotechnology in addressing the current challenges of energy conversion: 'high efficiency, stability, safety, and the potential for low-cost/scalable manufacturing' to quote from the contributed article by Nathan Lewis. This roadmap focuses on solar-to-fuel conversion, solar water splitting, solar photovoltaics and bio-catalysis. It includes dye-sensitized solar cells (DSSCs), perovskite solar cells, and organic photovoltaics. Smart engineering of colloidal quantum materials and nanostructured electrodes will improve solar-to-fuel conversion efficiency, as described in the articles by Waiskopf and Banin and Meyer. Semiconductor nanoparticles will also improve solar energy conversion efficiency, as discussed by Boschloo et al in their article on DSSCs. Perovskite solar cells have advanced rapidly in recent years, including new ideas on 2D and 3D hybrid halide perovskites, as described by Spanopoulos et al 'Next generation' solar cells using multiple exciton generation (MEG) from hot carriers, described in the article by Nozik and Beard, could lead to remarkable improvement in photovoltaic efficiency by using quantization effects in semiconductor nanostructures (quantum dots, wires or wells). These challenges will not be met without simultaneous improvement in nanoscale characterization methods. Terahertz spectroscopy, discussed in the article by Milot et al is one example of a method that is overcoming the difficulties associated with nanoscale materials characterization by avoiding electrical contacts to nanoparticles, allowing characterization during device operation, and enabling characterization of a single nanoparticle. Besides experimental advances, computational science is also meeting the challenges of nanomaterials synthesis. The article by Kohlstedt and Schatz discusses the computational frameworks being used to predict structure–property relationships in materials and devices, including machine learning methods, with an emphasis on organic photovoltaics. The contribution by Megarity and Armstrong presents the 'electrochemical leaf' for improvements in electrochemistry and beyond. In addition, biohybrid approaches can take advantage of efficient and specific enzyme catalysts. These articles present the nanoscience and technology at the forefront of renewable energy development that will have significant benefits to society.

Andrew Maicke et al 2024 Nanotechnology 35 275204

Perpendicular magnetic tunnel junction (pMTJ)-based true-random number generators (RNGs) can consume orders of magnitude less energy per bit than CMOS pseudo-RNGs. Here, we numerically investigate with a macrospin Landau–Lifshitz-Gilbert equation solver the use of pMTJs driven by spin–orbit torque to directly sample numbers from arbitrary probability distributions with the help of a tunable probability tree. The tree operates by dynamically biasing sequences of pMTJ relaxation events, called 'coinflips', via an additional applied spin-transfer-torque current. Specifically, using a single, ideal pMTJ device we successfully draw integer samples on the interval [0, 255] from an exponential distribution based on p -value distribution analysis. In order to investigate device-to-device variations, the thermal stability of the pMTJs are varied based on manufactured device data. It is found that while repeatedly using a varied device inhibits ability to recover the probability distribution, the device variations average out when considering the entire set of devices as a 'bucket' to agnostically draw random numbers from. Further, it is noted that the device variations most significantly impact the highest level of the probability tree, with diminishing errors at lower levels. The devices are then used to draw both uniformly and exponentially distributed numbers for the Monte Carlo computation of a problem from particle transport, showing excellent data fit with the analytical solution. Finally, the devices are benchmarked against CMOS and memristor RNGs, showing faster bit generation and significantly lower energy use.

Xiuyun Zhao and Vesa-Pekka Lehto 2021 Nanotechnology 32 042002

Batteries are commonly considered one of the key technologies to reduce carbon dioxide emissions caused by the transport, power, and industry sectors. We need to remember that not only the production of energy needs to be realized sustainably, but also the technologies for energy storage need to follow the green guidelines to reduce the emission of greenhouse gases effectively. To reach the sustainability goals, we have to make batteries with the performances beyond their present capabilities concerning their lifetime, reliability, and safety. To be commercially viable, the technologies, materials, and chemicals utilized in batteries must support scalability that enables cost-effective large-scale production.

As lithium-ion battery (LIB) is still the prevailing technology of the rechargeable batteries for the next ten years, the most practical approach to obtain batteries with better performance is to develop the chemistry and materials utilized in LIBs—especially in terms of safety and commercialization. To this end, silicon is the most promising candidate to obtain ultra-high performance on the anode side of the cell as silicon gives the highest theoretical capacity of the anode exceeding ten times the one of graphite. By balancing the other components in the cell, it is realistic to increase the overall capacity of the battery by 100%–200%. However, the exploitation of silicon in LIBs is anything else than a simple task due to the severe material-related challenges caused by lithiation/delithiation during battery cycling. The present review makes a comprehensive overview of the latest studies focusing on the utilization of nanosized silicon as the anode material in LIBs.

Latest articles

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Transparent heaters (THs) find widespread application in various indoor and outdoor settings, such as LCD panels and motorcycle helmet visors. Among the materials used for efficient TH performance, the AgNW network stands out due to its high conductivity, substantial transmittance, and minimal solution requirement. Extensive research has been directed towards enhancing AgNW characteristics, focusing on smaller diameters and longer wires. In TH applications, the primary considerations include a rapid response and elevated temperature. Consequently, this research delves into investigating the impact of parameters like diameter, length, and density on random AgNW networks under varying applied voltages. The finite element method is employed for analyzing temperature changes in response to voltage application, particularly in scenarios involving small-scale setups with high-density and high-percolation AgNW networks. The results reveal a significant increase in the thermal transition rate, ranging from 28% to 36%, with varying densities in the random network. Within the same density, the AgNW network with larger diameters and lengths demonstrates the highest temperatures, aligning with previous calculations. Furthermore, a trade-off exists between optical properties in smaller diameters and electrical properties in larger diameters within a relatively narrow temperature range.

Robert Daly et al 2024 Nanotechnology 35 285704

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has found application in the trace detection of a wide range of contaminants. In this paper, we report on the fabrication of 2D silver nanodendrites, on silicon chips, synthesized by electrochemical reduction of AgNO 3 at microelectrodes. The formation of nanodendrites is tentatively explained in terms of electromigration and diffusion of silver ions. Electrochemical characterization suggests that the nanodendrites do not stay electrically connected to the microelectrode. The substrates show SERS activity with an enhancement factor on the order of 10 6 . Density functional theory simulations were carried out to investigate the suitability of the fabricated substrate for pesticide monitoring. These substrates can be functionalized with cyclodextrin macro molecules to help with the detection of molecules with low affinity with silver surfaces. A proof of concept is demonstrated with the detection of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

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Sheraz Ahmad et al 2024 Nanotechnology 35 285401

The discovery of novel electrode materials based on two-dimensional (2D) structures is critical for alkali metal-ion batteries. Herein, we performed first-principles computations to investigate functionalized MXenes, Mo 2 BT 2 (T = O, S), which are also regarded as B-based MXenes, or named as MBenes, as potential anode materials for Li-ion batteries and beyond. The pristine and T-terminated Mo 2 BT 2 (T = O, S) monolayers reveal metallic character with higher electronic conductivity and are thermodynamically stable with an intrinsic dipole moment. Both Mo 2 BO 2 and Mo 2 BS 2 monolayers exhibit high theoretical Li/Na/K storage capacity and low ion diffusion barriers. These findings suggest that functionalized Mo 2 BT 2 (T = O, S) monolayers are promising for designing viable anode materials for high-performance alkali-ion batteries.

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Review articles

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Hao Liu et al 2024 Nanotechnology 35 242003

Over the past few decades, single-element semiconductors have received a great deal of attention due to their unique light-sensitive and heat-sensitive properties, which are of great application and research significance. As one promising material, selenium, being a typical semiconductor, has attracted significant attention from researchers due to its unique properties including high optical conductivity, anisotropic, thermal conductivity, and so on. To promote the application of selenium nanomaterials in various fields, numerous studies over the past few decades have successfully synthesized selenium nanomaterials in various morphologies using a wide range of physical and chemical methods. In this paper, we review and summarise the different methods of synthesis of various morphologies of selenium nanomaterials and discuss the applications of different nanostructures of selenium nanomaterials in optoelectronic devices, chemical sensors, and biomedical applications. Finally, we discuss possible challenges for selenium nanodevices and provide an outlook on the future applications of selenium nanomaterials.

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Accepted manuscripts

Cai et al 

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Zhou et al 

The overuse of antibiotics currently results in the presence of various antibiotics being detected in water bodies, which poses potential risks to human health and the environment. Therefore, it is highly significant to remove antibiotics from water. In this study, we developed novel rod-like NiCo-phyllosilicate hybrid catalysts on calcined natural zeolite (NiCo@C-zeolite) via a facile one-pot process. The presence of the zeolite served as both a silicon source and a support, maintaining a high specific surface area of the NiCo@C-zeolite. Remarkably, NiCo@C-zeolite exhibited outstanding catalytic performance in antibiotic degradation under PMS activation. Within just 5 min, the degradation rate of metronidazole (MNZ) reached 96.14%, ultimately achieving a final degradation rate of 99.28%. Furthermore, we investigated the influence of catalyst dosage, PMS dosage, MNZ concentration, initial pH value, and various inorganic anions on the degradation efficiency of MNZ. The results demonstrated that NiCo@C-zeolite displayed outstanding efficacy in degrading MNZ under diverse conditions and maintained a degradation rate of 94.86% at 60 min after three consecutive cycles of degradation. Free radical quenching experiments revealed that SO•− 4 played a significant role in the presence of NiCo@C-zeolite-PMS system. These findings indicate that the novel rod-like NiCo-phyllosilicate hybrid catalysts had excellent performance in antibiotic degradation.

He et al 

In this paper, a new Janus-structured nano drug delivery carrier Fe3O4@TiO2&mSiO2 was designed and synthesized, which consisted of a spherical head and a closely connected rod. The head was a nanocomposite of core/shell structure with magnetic spinel ferric tetraoxide core and anatase titanium dioxide shell (Fe3O4@TiO2), and the rod was ordered mesoporous silica (mSiO2). The nanocarriers showed excellent magnetic targeting capability (saturation magnetization, 25.18 emu g-1). The core/shell heads endowed the carriers with fine microwave responsiveness. The pore volume of mesoporous nanocarriers was 0.101 cm3 g-1, and the specific surface area was 489.0 m2 g-1. Anticancer drug doxorubicin could be loaded in the mesoporous of the carriers to form Fe3O4@TiO2&mSiO2-DOX. The drug loading capacity was 10.4%. Fe3O4@TiO2&mSiO2-DOX exhibited acid-sensitive and microwavesensitive release properties along with good bio-compatibility. Fe3O4@TiO2&mSiO2 Janus nanoparticles are expected to be ideal drug carriers.

Xie et al 

Selective and sensitive detection of volatile organic compounds (VOCs) holds paramount importance in real-world applications. This study proposes an innovative approach utilizing a single ReS2 field-effect transistor (FET) characterized by distinct in-plane anisotropy, specifically tailored for VOC recognition. The unique responses of ReS2, endowed with robust in-plane anisotropic properties, demonstrate significant difference along the a-axis and b-axis directions when exposed to four kinds of VOCs: acetone, methanol, ethanol, and IPA. Remarkably, the responses of ReS2 were significantly magnified under ultraviolet (UV) illumination, particularly in the case of acetone, where the response amplified by 10-15 times and the detection limit decreasing from 70 ppm to 4 ppm compared to the dark conditions. Exploiting the discernible variances in responses along the a-axis and b-axis under both UV and dark conditions, the data points of acetone, ethanol, methanol and IPA gases were clearly separated in the principal component space without any overlap through principal component analysis (PCA), indicating that the single ReS2 FET has a high ability to distinguish various gas species. The exploration of anisotropic sensing materials and light excitation strategies can be applied to a broad range of sensing platforms based on 2D materials for practical applications.

Almarzooqi et al 

Graphene oxide (GO)-based membranes hold significant promise for applications ranging from energy storage to protective coatings, to saline water and produced water treatment, owing to their chemical stability and unique barrier properties achieving a high selectivity for water permeation. However, unmodified GO membranes are not stable when submerged in liquid water, creating challenges with their commercial utilization in aqueous filtration and pervaporation applications. To mitigate this, we develop an approach to modify GO membranes through a combination of low temperature thermal reduction and metal cation crosslinking. We demonstrate that Zn2+–rGO and Fe3+–rGO membranes had the highest permeation flux of 8.3 ±1.5 L m-2 h-1 and 
7.0 ± 0.4 L m-2 h-1, for saline water separation, respectively, when thermally reduced after metal cross-linking; These membranes maintained a high flux of 7.5 ± 0.7 L m-2 h-1, and 5.5 ± 0.3 L m-2 h-1 for produced water separation, respectively. All the membranes had a salt rejection higher than 99%. Fe3+ crosslinked membranes presented the highest organic solute rejections for produced water of 69%. Moreover, long term pervaporation testing was done for the Zn2+–rGO membrane for 12 hours, and only a minor drop of 6% in permeation flux in permeation flux was observed, while Zn2+–GO had a drop of 24%. Both modifiers significantly enhanced the stability with Fe3+–rGO membranes display the highest mechanical abrasion resistance of 95% compared to non-reduced and non-crosslinked GO. Improved stability for all samples also led to higher selectivity to water over organic contaminants and only slightly reduced water flux across the membrane.

More Accepted manuscripts

Open access

Khalfan Almarzooqi et al 2024 Nanotechnology

Sabreen Jarrar et al 2024 Nanotechnology

Carbon-based electrode materials have widely been used in supercapacitors. Unfortunately, the fabrication of the supercapacitors includes a polymeric binding material that leads to an undesirable addition of weight along with an increased charge transfer resistance. Herein, binder-free and lightweight electrodes were fabricated using a powder processing of carbon nanofibers (CNFs) and graphene nanoplatelets (GNPs) resulting in hybrid all-carbon composite material. The structural, morphological, and electrochemical properties of the composite electrodes were studied at different concentrations of GNPs. The specific capacitance (Cs) of the CNFs was improved by increasing the concentration of GNPs in the composite. A maximum Cs of around 120 F g−1 was achieved at 90 wt.% GNPs which is around 5-fold higher in value than the pristine CNFs in 1 M KOH, which then further increased to 189 F g−1 in 6 M KOH electrolyte. The energy density of around 20 Wh kg−1 with the corresponding power density of 340 W kg−1 was achieved in the supercapacitor containing 90 wt.% GNPs. The enhanced electrochemical performance of the composite is related to the presence of a synergistic effect and the CNFs establishing conductive/percolating networks. Such binder-free all-carbon electrodes can be a potential candidate for next-generation energy applications.

Justinas Jorudas et al 2024 Nanotechnology

Fifty percents absorption by thin film, with thickness is much smaller than the skin depth and optical thickness much smaller than the wavelength, is a well-known concept of classical electrodynamics. This is a valuable feature that has been numerously widely explored for metal films, while chemically inert nanomembranes are a real fabrication challenge. Here we report the 20 nm-thin pyrolyzed carbon film (PyC) placed on 300 nm-thick silicon nitride (Si3N4) membrane demonstrating an efficient broadband absorption in the terahertz and near infrared ranges. While the bare Si3N4 membrane is completely transparent in the THz range, the 20 nm thick PyC layer increases the absorption of the PyC coated Si3N4 membrane to 40%. The reflection and transmission spectra in the near infrared region reveal that the PyC film absorption persists to a level of at least 10% of the incident power. Such a broadband absorption of the PyC film opens new pathways toward broadband bolometric radiation detectors.

Min Fu and Kevin Critchley 2024 Nanotechnology

Inkjet printing (IJP) has become a versatile, cost-effective technology for fabricating organic and hybrid electronic devices. Heavy-metal-based quantum dots (HM QDs) play a significant role in these inkjet-printed devices due to their excellent optoelectrical properties. Despite their utility, the intrinsic toxicity of HM QDs limits their applications in commercial products. To address this limitation, developing alternative HM-free quantum dots (HMF QDs) that have equivalent optoelectronic properties to HM QD is a promising approach to reduce toxicity and environmental impact. This article comprehensively reviews HMF QD-based devices fabricated using IJP methods. The discussion includes the basics of IJP technology, the formulation of printable HMF QD inks, and solutions to the coffee ring effect (CRE). 

Additionally, this review briefly explores the performance of typical state-of-the-art HMF QDs and cutting-edge characterization techniques for QD inks and printed QD films. The performance of printed devices based on HMF QDs is discussed and compared with those fabricated by other techniques. In the conclusion, the persisting challenges are identified, and perspectives on potential avenues for further progress in this rapidly developing research field are provided.

Sunaan Malik et al 2024 Nanotechnology

Paper is an ideal substrate for the development of flexible and environmentally sustainable ubiquitous electronic systems. When combined with nanomaterial-based devices, it can be harnessed for various Internet-of-Things applications, ranging from wearable electronics to smart packaging. However, paper remains a challenging substrate for electronics due to its rough and porous nature. In addition, the absence of established fabrication methods is impeding its utilization in wearable applications. Unlike other paper-based electronics with added layers, in this study, we present a scalable spray-lithography on a commercial paper substrate. We present a non-vacuum spray-lithography of chemical vapor deposition (CVD) single-layer graphene (SLG), carbon nanotubes (CNTs), and perovskite quantum dots (QDs) on a paper substrate. This approach combines the advantages of two large-area techniques: CVD and spray-coating. The first technique allows for the growth of SLG, while the second enables the spray coating of a mask to pattern CVD SLG, electrodes (CNTs), and photoactive (QDs) layers. We harnessed the advantages of perovskite QDs in photodetection, leveraging their strong absorption coefficients. Integrating them with the graphene enhanced the photoconductive gain mechanism, leading to high external responsivity. The presented device shows high external responsivity of ~520A/W at 405nm at <1V bias due to photoconductive gain mechanism. The prepared paper-based photodetectors (PDs) achieved an external responsivity of 520 A/W under 405 nm illumination at <1V operating voltage. To the best of our knowledge, our devices have the highest external responsivity amongst paper-based PDs. By fabricating arrays of PDs on a paper substrate in the air, this work highlights the potential of this scalable approach for enabling ubiquitous electronics on paper.

Hon Nhien Le et al 2024 Nanotechnology

Graphene oxide nanosheet (GO) is a multifunctional platform for binding with nanoparticles and stacking with two dimensional substrates. In this study, GO nanosheets were sonochemically decorated with zinc oxide nanoparticles (ZnO) and self-assembled into a hydrogel of GO-ZnO nanocomposite. The GO-ZnO hydrogel structure is a bioinspired approach for preserving graphene-based nanosheets from van der Waals stacking. X-ray diffraction analysis (XRD) showed that the sonochemical synthesis led to the formation of ZnO crystals on GO platforms. High water content (97.2 %) of GO-ZnO hydrogel provided good property of ultrasonic dispersibility in water. Ultraviolet-visible spectroscopic analysis (UV-Vis) revealed that optical band gap energy of ZnO nanoparticles (~ 3.2 eV) GO-ZnO nanosheets (~ 2.83 eV). Agar well diffusion tests presented effective antibacterial activities of GO-ZnO hydrogel against gram-negative bacteria (E. coli) and gram-positive bacteria (S. aureus). Especially, GO-ZnO hydrogel was directly used for brush painting on biodegradable polylactide (PLA) thin films. Graphene-based nanosheets with large surface area are key to van der Waals stacking and adhesion of GO-ZnO coating to the PLA substrate. The GO-ZnO/PLA films were characterized using photography, light transmittance spectroscopy, coating stability, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopic mapping (EDS), antibacterial test and mechanical tensile measurement. Specifically, GO-ZnO coating on PLA substrate exhibited stability in aqueous food simulants for packaging application. GO-ZnO coating inhibited the infectious growth of E. coli biofilm. GO-ZnO/PLA films had strong tensile strength and elastic modulus. As a result, the investigation of antibacterial GO-ZnO hydrogel and GO-ZnO coating on PLA film is fundamental for sustainable development of packaging and biomedical applications.

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• 1990-present Nanotechnology doi: 10.1088/issn.0957-4484 Online ISSN: 1361-6528 Print ISSN: 0957-4484

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Nanoscale doping of polymeric semiconductors with confined electrochemical ion implantation

A simple manipulation of an electrolyte’s glass transition enables nanoresolved electrochemical ion implantation doping in a variety of polymeric semiconductors.

• Lanyi Xiang

Nanosurface-reconstructed perovskite for highly efficient and stable active-matrix light-emitting diode display

Acid-etching-driven nanosurface reconstruction of perovskite quantum-dot pure-red LEDs facilitates a peak external quantum efficiency of 28.5% and a half-lifetime of 30 h at 100 cd m −2 luminance, enabling highly efficient solution-processed active-matrix perovskite displays.

• Yifeng Feng

Upconversion electroluminescence in 2D semiconductors integrated with plasmonic tunnel junctions

Plasmonic tunnel junctions integrated with a monolayer semiconductor are found to emit photons with energies exceeding the input electrical potential. This peculiar phenomenon is ascribed to being triggered by inelastic electron tunnelling dipoles inducing optically forbidden transitions in the carrier injection electrode.

• Vijith Kalathingal

Nanoparticles subdue antibiotic-resistant bacteria’s defences while enhancing innate immunity

A method for overcoming antibiotic resistance uses multimodal nanoparticles that target bacterial defence mechanisms while enhancing the innate immune response.

• Julia C. Lang
• Keira Melican

Multimodal nanoimmunotherapy engages neutrophils to eliminate Staphylococcus aureus infections

Antimicrobial resistance is becoming more prevalent. Here the authors use multimodal nanoparticles to modulate the infected microenvironment, recruit neutrophils and alleviate hypoxia to restore neutrophil function, demonstrating therapeutic efficacy against MRSA infections in mice.

• Jingcheng Zhu
• Shaoqin Gong

Giant nanomechanical energy storage capacity in twisted single-walled carbon nanotube ropes

A single-walled carbon nanotube spring stores three times more mechanical energy than a lithium-ion battery, while offering wide temperature stability and posing no explosion risk.

• Shigenori Utsumi
• Sanjeev Kumar Ujjain
• Katsumi Kaneko

Acute, controlled inhalation of thin graphene oxide nanosheets in humans with null cardiorespiratory effects

A double-blind, randomized, controlled human exposure trial of highly purified and thin nanometre-sized graphene oxide nanosheets shows that acute inhalation of aerosolized nanoparticles is not associated with harmful effects in healthy humans.

De novo design of pH-responsive self-assembling helical protein filaments

Engineering the tunability of protein assembly in response to pH changes within a narrow range is challenging. Here the authors report the de novo computational design of pH-responsive protein filaments that exhibit rapid, precise, tunable and reversible assembly and disassembly triggered by small pH changes.

• Eric M. Lynch
• David Baker

Roeland Nolte (1944–2024)

• Pall Thordarson
• E. W. Meijer

Light manipulation with sub-pixel wavefront control using gap phases

How can light be efficiently manipulated below the single-pixel level? An answer is now provided using near-field interactions for nanopillars in a metasurface — phase gradients in the gaps between the nanopillars constitute a new degree of freedom that enables efficient wavefront control at the nanoscale.

Highly efficient vortex generation at the nanoscale

A metasurface consisting of merely four nanopillars at the wavelength scale is sufficient to generate a high-quality vortex beam.

• Qinmiao Chen
• Shumin Xiao

Artificial intelligence assists the synthesis of all-natural plastic substitutes

Robotics and machine learning are combined to predict and prepare a variety of nanocomposite materials with properties mimicking those of various types of plastics, starting from natural building blocks.

• Zhaoming Liu

Controlling the STING pathway to improve immunotherapy

A genetically engineered variant of the stimulator of interferon genes (STING) protein is delivered to cancer cells, showing potential for clinical impact.

• John T. Wilson

Topographic fingerprinting of single proteins and proteoforms

A distance-based mapping strategy using single-molecule fluorescence resonance energy transfer via DNA eXchange (FRET X) enables full-length fingerprinting of intact protein sequences.

• J. Carlos Penedo

Graphene edge interference improves single-molecule transistors

The performance of three-terminal molecular transistors is enhanced through the harnessing of quantum interference in the edges of graphene electrodes.

• Héctor Vázquez

Quantum interference enhances the performance of single-molecule transistors

An experimental demonstration of how destructive quantum interference effects can increase the performance of single-molecule field-effect transistors to reach levels similar to those of nanoelectronic transistors.

• Zhixin Chen
• Iain M. Grace
• James O. Thomas

Engineering colloidal semiconductor nanocrystals for quantum information processing

This Review highlights the current potential for colloidal quantum dots for applications in quantum sensing and quantum circuits.

• Jawaher Almutlaq
• Edward H. Sargent

Engineering interfacial polarization switching in van der Waals multilayers

Operando transmission electron microscopy imaging reveals that modifying interlayer rotations alters both the spatial arrangement and switching dynamics of polar domains in artificially stacked trilayers of WSe 2 .

• Madeline Van Winkle
• Nikita Dowlatshahi
• D. Kwabena Bediako

Genome-wide forward genetic screening to identify receptors and proteins mediating nanoparticle uptake and intracellular processing

Understanding how cells process nanoparticles is crucial to improve nanomedicine efficacy. Here a genome-wide screening is used to discover proteins that are involved in silica nanoparticle accumulation by cells and shows that different apolipoprotein receptors and proteoglycans mediate their internalization.

• Daphne Montizaan
• Roberta Bartucci
• Anna Salvati

Author Correction: 3D nanofabricated soft microrobots with super-compliant picoforce springs as onboard sensors and actuators

• Oliver G. Schmidt

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Current Research in Nanotechnology peer reviewed journal for publication of research / review articles in the field of matter on an atomic and molecular scale. CRN covers diverse areas ranging from novel extensions of conventional device physics, to completely new approaches based upon molecular self-assembly, to developing new materials with dimensions on the nanoscale.

Science Publications is pleased to announce the launch of a new open access journal, Journal of Adaptive Structures. JAS brings together emerging technologies for adaptive smart structures, including advanced materials, smart actuation, sensing and control, to pursue the progressive adoption of the major scientific achievements in this multidisciplinary field on-board of commercial aircraft.

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Synergistic interaction of nanoparticles and probiotic delivery: A review

• Vijayaram, Srirengaraj
• Razafindralambo, Hary
• Sun, Yun Zhang
• Piccione, Giuseppe
• Multisanti, Cristiana Roberta
• Faggio, Caterina

Nanotechnology is an expanding and new technology that prompts production with nanoparticle‑based (1–100 nm) organic and inorganic materials. Such a tool has an imperative function in different sectors like bioengineering, pharmaceuticals, electronics, energy, nuclear energy, and fuel, and its applications are helpful for human, animal, plant, and environmental health. In exacting, the nanoparticles are synthesized by top‑down and bottom‑up approaches through different techniques such as chemical, physical, and biological progress. The characterization is vital and the confirmation of nanoparticle traits is done by various instrumentation analyses like UV–Vis spectrophotometry (UV–Vis), Fourier transform infrared spectroscopy, scanning electron microscope, transmission electron microscopy, X‑ray diffraction, atomic force microscopy, annular dark‑field imaging, and intracranial pressure. In addition, probiotics are friendly microbes which while administered in sufficient quantity confer health advantages to the host. Characterization investigation is much more significant to the identification of good probiotics. Similarly, haemolytic activity, acid and bile salt tolerance, autoaggregation, antimicrobial compound production, inhibition of pathogens, enhance the immune system, and more health‑beneficial effects on the host. The synergistic effects of nanoparticles and probiotics combined delivery applications are still limited to food, feed, and biomedical applications. However, the mechanisms by which they interact with the immune system and gut microbiota in humans and animals are largely unclear. This review discusses current research advancements to fulfil research gaps and promote the successful improvement of human and animal health.

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Title: a survey on the memory mechanism of large language model based agents.

Abstract: Large language model (LLM) based agents have recently attracted much attention from the research and industry communities. Compared with original LLMs, LLM-based agents are featured in their self-evolving capability, which is the basis for solving real-world problems that need long-term and complex agent-environment interactions. The key component to support agent-environment interactions is the memory of the agents. While previous studies have proposed many promising memory mechanisms, they are scattered in different papers, and there lacks a systematical review to summarize and compare these works from a holistic perspective, failing to abstract common and effective designing patterns for inspiring future studies. To bridge this gap, in this paper, we propose a comprehensive survey on the memory mechanism of LLM-based agents. In specific, we first discuss ''what is'' and ''why do we need'' the memory in LLM-based agents. Then, we systematically review previous studies on how to design and evaluate the memory module. In addition, we also present many agent applications, where the memory module plays an important role. At last, we analyze the limitations of existing work and show important future directions. To keep up with the latest advances in this field, we create a repository at \url{ this https URL }.

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COVID-19 virus disrupts protein production: Researcher discusses her recent findings

by Jenni Bozec, University of Toronto

Despite huge advances in our understanding of COVID-19 over the past four years, the disease is still very much among us—and there remains a lot to learn.

One thing we do know: Following infection, it's critical that our cells make new proteins to defend against the virus.

But Talya Yerlici, a post-doctoral researcher at the University of Toronto's Temerty Faculty of Medicine, recently showed how SARS-CoV-2 disrupts the manufacture of proteins.

She is the first author of a paper detailing the process that was published recently in the journal Cell Reports .

Writer Jenni Bozec recently spoke with Yerlici—who is based in the lab of Professor Karim Mekhail in the department of laboratory medicine and pathobiology—about the findings.

What have you discovered about how COVID-19 uses proteins?

One way SARS-CoV-2 makes us sick is by using a strategy called "host shutoff." This means that while the virus makes copies of itself, it also slows the production of vital components within our cells. As a result, our bodies take longer to respond to the infection.

When SARS-CoV-2 enters our cells, it disrupts the process of making proteins, which are essential for our cells to work correctly. A particular SARS-CoV-2 protein called Nsp1 has a crucial role in this process. It stops ribosomes, the machinery that makes proteins, from doing their job effectively. The virus is like a clever saboteur inside our cells, making sure its own needs are met while disrupting our cells' ability to defend themselves.

We found that Nsp1 is good at blocking ribosomes from making new proteins, but also interferes with the production of new ribosomes. In effect, it shuts down the machinery output and the ability to make the machinery itself—a serious double hit.

It does this by blocking the maturation or processing of specialized RNA molecules needed to build ribosomes. This adds a new layer of complexity to our understanding of SARS-CoV-2's interference with the host cell.

How could this discovery impact treatment for those with COVID-19?

Building on our published research, it will be crucial to understand how Nsp1 works to stop different types of human cells, tissues and organs from making proteins when infected with different variants of SARS-CoV-2 and related coronaviruses.

Scientists have been working to find precision medicines that can counteract Nsp1 and help fight against the continually evolving SARS-CoV-2 virus. These drugs aim to help infected cells keep producing proteins and build a robust immune response when dealing with infection. Ongoing research on such drugs should now benefit from testing whether they can block Nsp1 from interfering with both the production and function of ribosomes, and this should help find more effective precision medicines.

What drew you to this line of research?

This project started because of circumstances during the COVID lockdown. We wanted to help in the fight against the pandemic. However, since I couldn't physically work in the lab, we took the opportunity to analyze next-generation sequencing datasets computationally from home.

Looking at published RNA-sequencing datasets, we realized that cells infected with SARS-CoV-2, compared to uninfected cells, may have difficulty processing the RNA molecules needed to build ribosomes. Through this analysis, together with Dr. Mekhail, we developed hypotheses and designed the project.

I had the privilege of collaborating closely with the talented members of the Mekhail lab, including Alexander Palazzo's group from the department of biochemistry at Temerty Medicine and Brian Raught and Razqallah Hakem's labs at the Princess Margaret Cancer Center (University Health Network).

This work wouldn't have been possible without the collective efforts of our team and collaborators, and I'm grateful for their contributions. My responsibilities included conducting numerous hands-on experiments and bioinformatics analyses, analyzing the results and preparing the paper for peer review and publication.

What were the most challenging and rewarding aspects of this project?

The most challenging part was conducting research during a global pandemic, which presented many logistical hurdles—from disrupted lab routines to limitations on collecting and using samples infected with SARS-CoV-2.

On the other hand, the opportunity to contribute to our understanding of SARS-CoV-2 viral mechanisms and shed light on potential therapeutic targets was incredibly fulfilling. Seeing our research culminate in a published paper and knowing it could inform future strategies for combating coronaviruses is deeply gratifying.

What are your longer-term goals as a scientist?

As an independent investigator in my future lab, I want to study how the complex processes of making ribosomes affect the body's natural defense against viruses. It's an area I find compelling and presents ample opportunities for further exploration.

One approach I'm particularly interested in is integrating RNA-sequencing with genetic CRISPR and small-molecule chemical screens, targeting distinct stages of ribosome biogenesis across diverse infection or infection-mimicking conditions.

Such integrated approaches hold promise for uncovering novel mechanisms underlying the regulation of antiviral responses and should help us find innovative and impactful ways to fight viral infections.

Journal information: Cell Reports

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Nanotechnology Advances in the Detection and Treatment of Cancer: An Overview

Sareh mosleh-shirazi.

1 Department of Materials Science and Engineering, Shiraz University of Technology, Shiraz, Iran

Milad Abbasi

2 Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

Mohammad reza Moaddeli

3 Assistant Professor, Department of Oral and Maxillofacial Surgery, School of Dentistry, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

4 Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran

Mostafa Shafiee

Seyed reza kasaee.

5 Shiraz Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Ali Mohammad Amani

Saeid hatam.

6 Assistant Lecturer, Azad University, Zarghan Branch, Shiraz, Iran

7 ExirBitanic, Science and Technology Park of Fars, Shiraz, Iran

Over the last few years, progress has been made across the nanomedicine landscape, in particular, the invention of contemporary nanostructures for cancer diagnosis and overcoming complexities in the clinical treatment of cancerous tissues. Thanks to their small diameter and large surface-to-volume proportions, nanomaterials have special physicochemical properties that empower them to bind, absorb and transport high-efficiency substances, such as small molecular drugs, DNA, proteins, RNAs, and probes. They also have excellent durability, high carrier potential, the ability to integrate both hydrophobic and hydrophilic compounds, and compatibility with various transport routes, making them especially appealing over a wide range of oncology fields. This is also due to their configurable scale, structure, and surface properties. This review paper discusses how nanostructures can function as therapeutic vectors to enhance the therapeutic value of molecules; how nanomaterials can be used as medicinal products in gene therapy, photodynamics, and thermal treatment; and finally, the application of nanomaterials in the form of molecular imaging agents to diagnose and map tumor growth.

Introduction

Oncologists worldwide, use a variety of treatments, including radiation therapy, surgery, and chemotherapy, to treat cancer patients 1 . But the treatment of a tumor tissue demands dealing with plenty of limitations that urge the increasing interest in the use of Nanomaterials. Over the last decade, increased knowledge of the microenvironment of tumors has motivated our efforts to develop nanoparticles as a novel cancer-related therapeutic and diagnostic strategy 2 . Cancer tissues consist of non-cellular (e.g. interstitial and vascular) or cellular compartments which vary considerably from the healthy tissues around them. Each of these compartments presents a challenge for the delivery of drugs to tumor cells locally (Figure ​ (Figure1) 1 ) 3 , 4 . However, tumor therapy through conventional methods brings more affordable choices for patients and many scientists still work on Click Chemistry-derived simple organic molecules such as Acridone to simplify the treatment procedure. On the other hand, it looks unavoidable to develop more efficient and less time-consuming treatments involved with nanostructures because of difficult delivery, low bioavailability, transportation issues, and hazards related to conventional drug molecules 5 .

The tumoral microenvironment. Angiogenesis is due to tumor cell release agents (e.g. bradykinin, vascular endothelial growth factor (VEGF), nitric oxide (NO), and prostaglandin (PG) that induce the development of fresh blood vessels (Top left). Tumor heterogeneity is seen in regions of tumor necrosis or tumor perfusion that contain active tumor cells that are strong and weak (Top Right). Representation of tumor cell drug resistance through the protein pumps responsible for removing chemotherapy drugs from the cell. Also, insufficient lymphatic cell penetration to tumor tissue (Bottom). Created with BioRender.com

Tumor vascularity is distinctly heterogeneous within its non-cellular composition. This includes extremely avascular regions that absurdly supply nutrients and oxygen for the rapid development of tumor components since tumor necrotic areas have a very limited blood supply. Tumor cells that are isolated far off the vascular system, as mentioned, have a reduced amount of oxygen available; this is mainly due to the additional gap between the tumor cells for which oxygen is to be distributed and also to the higher consumption of oxygen within the tumor cells that are closer to the circulatory system 6 , 7 . In a mechanism called angiogenesis, fresh blood vessels are reproducing around tumors; however, such vessels are abnormal with elevated percentages of endothelial cell proliferation, increased vascular tortuosity, and lack of pericytes. Also, there are considerable distances across the basement membrane between adjacent endothelial cells that vary from 380 to 780 nm. Bradykinin, prostaglandin and nitric oxide, vascular endothelial growth factors, are all up-regulated while resulting in a hyper permeable tumor cell condition (Figure ​ (Figure1) 1 ) 8 , 9 .

The interstitial environment, consisting of an elastic and collagen fiber network, surrounds the tumor cells. Tumor interstitium contains extreme intercellular stress and often a comparative lack of lymphatic activity in these areas, as opposed to regular tissues, which minimizes the extravagance of vasculature medications due to increased interstitial pressure around it 10 .

Overall, getting to know non-cellular pathways of drug tolerance appears to be necessary for the following reasons. The decrease in accessible oxygen due to the unavailability of the vasculature contributes to the acidic microenvironment resulting from the anaerobic glycolysis accumulation of lactic acid and, in particular, to the tolerance of simple ionized drugs, thus prohibiting their spread through cell membranes 11 , 12 .

Scientific investigations have demonstrated that there are two distinct cell populations within the tumor: a relatively small, unusual, and quiet group known as cancer stem cells (CSCs) and a larger group of rapidly proliferating cells that make up the bulk of the tumor mass 13 . While non-CSCs will not be metastatic or self-sustaining, CSCs can not only reconstruct the tumor but also maintain cell migration (e.g. metastases and invasion) and self-protection genetic machinery. This keeps the CSCs behind, which then rebuilds the tumor because most chemotherapy drugs mainly target non-CSCs which reveals why cancers sometimes recur after surgery 14 . Experimental drugs are therefore directly tailored to CSCs, which are now considered to be the key objective of therapeutic intervention. Death of CSCs, avoids local recurrence and metastases, and would thoroughly destroy cancer cells. In addition, it has also been shown that the microenvironment surrounding the CSCs regulates their proliferation, as well as their cell-fat functions, enabling tumors to demonstrate their total neoplastic phenotype. Another strategy for treating and attempting to control cancer progression could be techniques for modifying nonmalignant cells across the microenvironment 15 , 16 . One of the objectives of nano-delivery of drugs is to control the tumor-associated macrophages (TAMs), triggered by chemokines and other growth factors (e.g. colony-stimulating factor-1) provided by tumor cells to the mass of the tumor. TAMs are abundant throughout the solid tumor stroma and have been shown to intensify tumor development by facilitating the migration and invasiveness of tumor angiogenesis. This confirms the strong association between increased TAM penetration and negative patient outcomes 17 - 19 .

Current therapies concerning anti-angiogenesis include the use of organic and synthetic molecules such as pazopanib, regorafenib, and lenvatinib as mentioned in recent research 20 . However, repetitive reports show complicated resistance mechanisms to these drugs resulting from interactions between bone marrow stem cells, tumor cells, and local differentiated cells that give rise to tumor escape from antiangiogenic drugs 21 . Combining advanced nano-delivery systems with antiangiogenic drugs will less likely stimulate interstitial fluid pressure, provide more oxygenation inside the tumor microenvironment and further restrict drug resistance mechanisms 22 .

Biochemical and metabolic alterations in cancer cells lead to enzymatic functional abnormalities, apoptosis induction, and altering extracellular/ intracellular transport pathways, all of which lead to molecular processes associated with drug tolerance. Perhaps the most important example is the upregulation of MDR-related protein pumps, often recognized as P-glycoprotein, an ATP binding cassette transmitter that is qualified to extrude many chemotherapy agents through cell membranes, thus decreasing drug-target association 23 . Furthermore, due to the non-specific systemic bioavailability, the complete clinical advantage of certain therapeutic agents is impaired, resulting in systematic cytotoxic effects and reduced concentration of needed drugs specifically for tumors. In parallel with this, a recent analysis focuses on the development of more selective regional drug dissemination or drug-targeted intervention to address these barriers. In other words, current therapies require high-dose tumor chemotherapy drugs with minimal risk to healthy neighborhoods 24 , 25 . There are instances of monoclonal antibody-grafted medications that attach to molecular objectives mainly overexpressed across cancerous cells 26 , 27 . It, therefore, makes it easier to target drugs directly to the tumor while at the same time minimizing their distribution to healthy cells which will not strongly bind to the antibody. Experiments, however, have shown that only 1 to 10 parts per 100,000 monoclonal antibodies injected intravenously meet their parenchymal objectives in vivo, with comparable drawbacks for molecular diagnostic agents. The use of nanostructures for the release of therapeutic drugs, the treatment of tumors, and the follow-up of tumors using multiple imaging techniques is a recently evolving strategy to address these concerns 26 , 28 , 29 .

Unparalleled developments in the field of nanomedicine have taken place over the last few years, with the development of modern nanostructures for detection as well as therapeutic interventions for disorders such as cancer 30 . Despite their limited scale, nanomaterials have special physicochemical functions that cause nanostructures to have a surface-to-volume relationship that is also greater than most nanomaterials themselves. Thanks to its extensive usable surface area, some molecules, including tiny molecule medicines, probes, RNA, DNA, and proteins, can be attached, absorbed, and transported by nanostructures. Their controllable scale, surface, and configuration features further qualify nanomaterials to provide excellent durability, extreme volume, built-in functionality of hydrophilic and hydrophobic materials, and versatility with numerous routes of administration. The latter makes them extremely desirable in many areas of medical sciences (Figure ​ (Figure2) 2 ) 31 , 32 . While their physicochemical characteristics can be determined mainly during their design (e.g. shape and size) as well as the material from which nanostructures are produced, nanomaterials are generally reasonably durable across broad pH and temperature ranges. On the contrary, the absence of biodecomposition and also the slower release levels in some nanostructures raise alarms about their safety and health concerns, particularly during their prolonged implementation. Still, some nanostructures (e.g. lipids, phospholipids, chitosan, and dextran) may be classified as biological substances 33 , 34 , like carbon-based compounds (e.g. carbon nanotubes) 35 , while, there are inorganic nanostructures (e.g. metal oxides, metal-based compounds, and metal sulfides) 36 , 37 which further involve semiconductor nanostructures (e.g. quantum dots (QDs)) 38 With unique interactions with cells, based on their structure (Figure ​ (Figure2) 2 ) 32 , 39 , 40 .

Main Features of Nanoparticles. Different choices available to design a nanostructure based on what method is used to apply the nanomaterial in cancer therapy. Different surface coatings of nanoparticles (left side), different materials available to design nanoparticles (right side), and some of their general properties are shown. Created with BioRender.com.

This research explains how nanostructures can be employed in chemotherapeutic drug delivery systems to enhance their therapeutic efficacy; how they would be used as therapeutic drugs for thermal photodynamics and gene therapy; and how nanomaterials can be used as molecular diagnostic carriers to identify and track cancer development.

Nanostructures as carriers for drug molecules

The transmission of medications is one of the main fields in which nanotechnology continues to fundamentally change the cancer treatment process. Two primary aspects of nanostructures are currently evolving: nanostructure on its own being used as both carrier, and chemotherapeutic medicine 41 . Second, The medication may either be absorbed into the body directly, or dissolved within the nanoparticle framework, becoming covalently bound to the surface of the nanostructure 42 .

The investigation used by paclitaxel has shown that the formulation of drugs in form of nanostructures prolongs both its level of cytotoxic activity throughout cultured cells and its therapeutic efficacy in living animal models, as opposed to the traditional use of drugs 43 , 44 . This was due to higher biocompatibility, as well as the prolonged bioavailability of nanoparticles, which aids the drug dose to maintain above the required effective value over longer periods. Furthermore, the design of nanoparticles overcomes the problems associated with the re-implementation of paclitaxel including poor water solubility in media and extreme adverse effects associated with the Cremophor EL adjuvant 45 , 46 .

The following criteria for nanomaterial-drug systems must be met to effectively transfer their loads directly to cancerous cells inside organisms:

• To ensure the systematic distribution of drugs, the structure of the nanoparticle drug must remain constant throughout the serum.
• It is necessary to distribute the nanoparticle-drug matrix to tumor cells (either through enhanced permeability and retention (EPR) or through receptor-mediated interactions), thus reducing any unintended problems caused by non-targeted transmission.
• Nanostructures must have the potential to release drugs once they are located in the tumor.
• To ensure safe degradation, the remaining nanostructure carriers should preferably be constructed of a short-lived or biologically inert substance.

If, on the other hand, a non-biodegradable material is used, it must have been proved to be harmless at required levels or to be free from the source material 47 - 49 .

The complex of nanomaterial-medication

Nanostructures used as vectors will also bind to the medicine or encapsulate the medication to prevent both breakdown and denaturation 49 . Nanostructured materials carriers often provide the ability for hybrid treatment defined as the co-delivery of two or more drugs simultaneously 50 . New uses often require the transmission of non-cytotoxic prodrugs that can become functional after administration to cancer cells (e.g. platinum-centered chemotherapeutic substances [Pt]) and can be photo-reduced from their prodrug form Pt[IV] to functional Pt[II] antitumor agents when transmitted through visible light within cells using nanostructures 51 . There are many forms of nanostructures, namely solid lipid, liposomal, polymer-based, inorganic, and mesoporous silica nanomaterials used as carriers. Liposomes are biologically oriented nanostructures consisting primarily of amphipathic phospholipids enveloping an internal aqueous region formed by concentric self-assembly of a lipid bilayer (Figure ​ (Figure2) 2 ) 52 , 53 .

They are capable of storing hydrophilic drugs and maintaining an inner aqueous framework and therefore, are able to be configured for attachment to cell membranes during endocytosis and to continuously release medications. Research has shown improved pharmacokinetics and pharmacodynamics of liposome-related products. Liposomes have been surface-operated with polyethylene glycol (PEG) and glycolipids to inhibit their accelerated removal from systemic circulation through reticuloendothelial system phagocytic activity 54 , 55 . The introduction of PEG or other water-soluble conjugates on the outer surface of all types of nanostructured vectors, such as liposomes, improves the biological fluid stability of the nanostructure while at the same time producing a dynamic network of hydrophilic and neutral surface chains that reduces protein opsonization and enables nanomaterials to potentially escape RES macrophages (Figure ​ (Figure2) 2 ) 56 , 57 . This will improve the half-life of nanoparticles across the bloodstream, which, together with their ability to graft targets, will allow them to selectively concentrate at the tumor site. Although liposomes were initially thought to penetrate cells by merging their phospholipid membrane with cell membranes, the explanation for this mechanism is now assumed to be endocytosis (Figure ​ (Figure4 4 ) 58 , 59 . The medicinal effects of chemotherapy-filled liposomes, such as doxorubicin and daunorubicin, for the treatment of patients with hematological malignancies and solid tumors, are being studied in ongoing clinical trials 60 , 61 . Doxil refers to a PEG-decorated liposome filled with doxorubicin, which has been shown to improve pharmacokinetic properties as well as to decrease serious side effects compared to similar medications and doxorubicin alone. It has been authorized by the FDA to treat patients with metastatic breast and ovary as well as human immune patients with Kaposi sarcoma 62 , 63 .

Drug loading, cellular delivery, and release through liposome nanoparticles (left side. Also methods to prolonge the bioavailability and increase target specificity in liposome-based nanostructures are shown (right side). Created with BioRender.com

Solid lipid nanoparticles (SLNs) were advanced in the 1990s as a superseded carrier structure for liposomes, emulsions, and polymer-based nanostructures 64 . Due to their robust hydrophobic lipid core enclosed by monolayer phospholipids, they are much more durable than liposomes throughout biological processes (Figure ​ (Figure4 4 ) 65 . In these payload architectures, the benefits of colloidal lipid emulsions are often incorporated into solid particulates. Because they are often environmentally friendly, they become less hazardous than mesoporous silica or polymeric nanomaterials 66 . SLNs made up of 0.1-30% lipid matrix spread throughout the watery solution and remain stable at 0.5-5 percent of the surfactant when required 67 , 68 . Since it is straightforward to control the variables included in the SLN synthesis, the SLNs are being constructed using the following: 1) a drug-filled casing, 2) a drug-filled center, and 3) a uniform composition, with a specific release of drugs by each model 69 , 70 . Since drugs have often been seen at lower temperatures to penetrate the SLN whereas, to escape it at higher temperatures, methods of induction of hyperthermia may be used to charge and discharge SLNs with medicinal products 71 . A strongly organized crystal lattice does not handle large amounts of medication as integrated drugs are placed inside lipid layers, fatty acid chains, or inside crystal imperfections. Increased loading of drug1 is therefore feasible when using more specific lipids (e.g. monoglycerides, diglycerides, triglycerides, or separate chain lengths) 72 . Even so, for the lipid matrix, the drug loading potential of traditional SLNs is reduced to around 25%. Temperature changes can often contribute to polymorphic transformations during storage or delivery, which may cause the substance to be expelled prematurely from the lipid network (Figure ​ (Figure3) 3 ) 73 . To address these issues, besides increasing the payload of drugs and prohibiting the elimination of drugs, SLN variants have also been generated 74 .

Different assembly methods for Nanoscale delivery of small molecules. The capacity of each nanostructure to encapsulate drug molecules is shown. Created with BioRender.com

Although most nanostructures are based on polymers, in general, nanospheres and nanocapsules, are labels applied to any form of polymer nanoparticle 75 . While nanospheres typically become globular or rigid by substances bound to their exterior side, nanocapsules remain vesicular structures containing compounds enclosed inside a cavity with a solid shell covered by a liquid kernel (either oil or water) 76 . Polymer nanostructures may be manufactured through classical polymerization or polymeric reactions of constructed polymeric materials. The chemistry included in nanomaterial production may be effectively modified to allow them to attain desirable characteristics such as surface functionalization which itself, improves the characteristics of biodistribution and pharmacokinetic regulation. Research also indicated that the degree and magnitude of the release profile of nanomaterials can be precisely adjusted in relation to the volume of nanostructure absorbed into cells by specifically controlling the drug-to-polymer ratio as well as the polymeric structure and molecular mass 31 , 40 , 77 . For example, polylactic acid (PLA), poly(e-caprolactone), poly(lactide-coglycolide) (PLGA), polyglycolic acid and polyglycolic acid are biodegradable synthetic polymeric nanostructures (alkyl-cyanoacrylate) 78 - 80 .

Natural polymer compound examples include gelatin, dextran ester, and chitosan. Although they may only have adequate purity-related effectiveness or reproducibility relative to synthetic polymeric materials 81 . Over the past several decades, polymer-based nanostructures have also been researched for drug delivery applications. For instance, the FDA accepts environmentally friendly polymer-based nanostructures like PLGA and PLA for human use 78 , 82 . The application for paclitaxel attached to the organic polymer-based albumin nanostructure for the medical treatment of patients with metastatic breast cancer has also been approved by the FDA, while the polymer-based nanomaterial composition containing docetaxel is currently in the initial phase of clinical studies for patients with progressive solid malignancy 83 .

Mesoporous silica nanomaterials have also been extensively researched to evaluate their capability to maintain the drug bioavailability and prevent denaturation or degeneration of drug molecules due to their property in providing physical encasement. Mesoporous nanostructured surface openings could either contribute to a centralized container filled with a drug product and dynamic worms could shape nanomaterials themselves - like a channel system that allows a relatively large quantity of drugs to be distributed in a regulated manner. The distribution of pore sizes has also been shown to be helpful to evaluate the pharmacokinetic profile of the drug payload 84 , 85 . The investigation also evaluated the reversible coating of mesoporous silica nanomaterial outer side openings that mechanically minimized the unleash of medications until nanomaterials reached their zero early release target. Cadmium sulfide, by which disulfide-containing organs are chemically clearable by disulfide-reducing substances or nano-based iron oxide nanostructures is also investigated. Membrane-impermeable drugs may be distributed through such cargo structures, acting as an intracellular drug transporter and a tool for image processing operations 86 , 87 .

A wide variety of nanomaterial systems are made up of inorganic nanoparticles; metals, metal sulfides, and metal oxides. They are capable of being developed in form of prototypes with excellent reproducibility, varying in scale, shape, and pore size, and can be conveniently coupled with tumor-targeting ligands and chemotherapy drugs. Furthermore, in order to generate nanomaterials that can escape the RES, their surface structure can often be effectively modified 88 . They are fairly constant over wide ranges of temperature and pH, especially in comparison to liposomes and nanostructured solid lipid carriers (Figure ​ (Figure2). 2 ). However, their inadequacy of biodecomposition and their relatively low rate of degradation give rise to doubts about their post-delivery removal 89 , 90 .

The nanomaterial- medication complex's durability

The level of renal excretion or reticuloendothelial system (RES) activity affects the circulation of the blood throughout the kidney. Comparatively small nanomaterials are easily removed by the kidneys, while larger nanostructures are removed by RES. Nanomaterial capture of RES cells reduces their systematic bioavailability. Surface functionalization with water-soluble PEG chains will, however, offer "stealth-like" properties to nanostructures, culminating in their continuous presence throughout the bloodstream by decreasing the immune responses against them as well as preventing their detection and phagocytosis through the mononuclear phagocytic renal system 91 , 92 .

Besides, PEGylation seems to be necessary as "bare" nanomaterials, adsorbs proteins that allow them to accumulate in biological systems. This prohibits the solution accumulation of nanoparticles and the formation of clusters while entering the vascular system where they potentially embolize vessels and block the supply of blood to remote locations and organ systems leading to microinfarction 93 , 94 .

Tumor cell delivery of the nanoparticle-drug matrix

Nanomaterials may be delivered to tumors either passively or actively after introducing to the circulatory system. Nanostructures can benefit from the specific effect of EPR in tumors through passive transmission, which allows them to escape the bloodstream and reach the extravascular area where they localize close to solid tumors. Nanostructures should preferably be thinner than 100 nanometers to maximize their efficacy. Due to the variability in the bloodstream supply of a tumor mass, as well as bio-physiological limitations, and in some cases stiffness of the intercellular framework, the location of nanostructures within the tumor would not be consistent 95 . Instead, using surface functionalization, nanomaterials can effectively target tumors (e.g. binding of ligands including small molecules, peptides, oligosaccharides) 96 . An antigen or receptor may be the target substance, but it must strictly express over the malignant cells and express at close to zero or marginal thresholds for healthy cells. Nanomaterials are competent to improve the transfer of drugs by targeting tumor cells directly, while also helping to reduce the toxic effects of the free medicine on non-target tissues. thus, enhancing the quality of cancer treatment. The assessment has already shown that the attachment to multiple receptors at the same time contributes to the multivalent properties of nanostructures enhancing the ability to interact with cancer cell membranes 97 .

Examples include nanostructures attached to folate ligands that have a tenfold higher sensitivity to folate binding protein than free folate since folate receptors are also located on the surface of cancer cells in clusters. Besides, PEG chains attached to nanomaterials may also be functionalized by binding to tumor-specific conduits to enhance their bioavailability 98 , 99 .

Drug release from the nanomaterial-medicine framework

The nanomaterial-medication matrix should be broken after it has been delivered to the tumor site to activate the medication 100 .

Medications become free from nanostructures when attached to cancer cells either by leaking out of the frame or by swelling, erosion, and breakdown of nanomaterials. An innovative photo-engineered nanomaterials vehicle, for example, has recently been established that initiates a reversible shift in diameter when ultraviolet light is applied that facilitates the diffusion of therapeutic agents, thereby providing spatial and temporal drug release management 101 . However, the therapeutic implementation of this current technique may be severely hindered by insufficient absorption of ultraviolet radiation into the tissues. Additional systems are required for the desired features of hybrid nanostructures that enable a multi-stage delivery method. Thus, each of the different layers of the nanostructure reacts separately to the surrounding physiological systems in such a way that variations in pH, oxidative stress, or temperature (e.g. in the acid microenvironment of the tumor) can lead to variations in the structure of the nanostructure causing the release of pre-loaded therapeutic agents (Figure ​ (Figure5) 5 ) 102 , 103 . This change in diameter is caused by proteases primarily expressed in the microenvironment of the tumor. For example, the metalloproteinase-2 matrix deforms the nano properties of 100 nm gelatin 104 .

Removal of the main cancer cells. Cancer stem cell-specific markers serve as important drug targets for active targeting by nanoparticle-drug systems. Following the target-specific attachment of the nanostructure, drug release can be achieved using internal or external stimuli. Different choices for drug delivery and release are demonstrated in this picture. Created with BioRender.com

These properties are effective in the treatment of tumors that produce fibrillary collagen type I and type III throughout interstitial spaces. The latter thickens the extracellular matrix and causes fibrosis, impairing further spread and absorption of larger nanostructures 105 , 106 . The capacity of nanostructures that enable the controlled release of medications through their framework often resolves the challenges of drug release at fixed speeds regardless of the needs of the patient and the ever-changing tumor environment. The mechanism by which the drug release can be controlled allows the concentration of drugs to be maintained over a long period throughout their therapeutic window and also enables the use of multiple doses for a single treatment 107 . It was also proposed to help facilitate 'chrono-administration' of the drug 101 , in which it was speculated that the precise timing of the distribution of therapeutic agents was crucial in ensuring optimum therapeutic impact in order to optimize tumor destruction and reduce metastatic spread. When released from the nanomaterials, the next obstacle for most chemotherapy agents is now to spread within cancer cells to affect targeted substances in intracellular media. It is difficult to see how quickly medications can penetrate the cellular environment, either through activated delivery processes or through receptor-facilitated endocytosis mechanisms, and how limited their distribution is in the proximity of cancer tissues 108 . Some researchers are therefore designing techniques whereby the whole drug-nanoparticle structure may penetrate cancer cells before the actual release of pharmacological drugs into the cytosol to improve the accuracy of drug distribution to appropriate intracellular targets 108 , 109 . They are working to promote intracellular absorption by marking nanomaterials with peptides to penetrate the cells, like Penetration and anti-actin-targeting substances such as transcription transactivator (TAT) peptide in accompanying with a nice arrow peptide 110 , 111 . As most of the mentioned compounds have main objectives inside the cells, they are anticipated to have a stronger therapeutic impact. In addition, this is particularly advantageous for medications that are often quickly ejected by cells utilizing membrane transporters, including protein-based pumps correlated with multidrug resistance, and it is shown that P-glycoprotein often acts by detecting drugs that need to be expelled outside the cells, especially when they are found inside cell membranes 112 . The chemical composition of the nanostructure will contribute to the release of drugs once they reach inside the cell. For example, when medicines are grafted with nanomaterials through thiol groups, these nanostructures can be replaced with glutathione, which remains widely available throughout the cytosol, leading to the unleashing of almost any trapped medication 113 . In situations where the nanomaterial-medication framework is not directly absorbed or internalized into cancer cells as a whole, the drug could now be transported out of the cell, apart from the nanostructure, where it could then reach the cell through direct diffusion and possibly other transport mechanisms 91 . The downside of this drug distribution system is that a large amount of the drug will be redistributed to the natural tissues around it, thus reducing its efficacy in the treatment. Furthermore, since the interstitial atmosphere surrounding the tumor is acidic, it, therefore, produces a hazardous microenvironment for the transmission of medicines that decreases the efficacy of alkaline chemotherapy drugs.

Elimination of the remaining nanostructure after release

Most of the nanoparticle drug structures produced has been made up of environmentally friendly substances (e.g. lipids, phospholipids, chitosan, and dextran) which allow the drug to be released once the nanomaterial container has been degraded 114 , 115 . Non-biological vectors are therefore reasonably stable through high pH and temperatures, and the latter include inorganic nanostructured materials. But this is of major concern for their lack of post-drug release transmission, biodecomposition, and biodegradation 39 , 116 . Therefore, whenever these non-biological products are used, they must be properly eliminated from the body's environment or maintained in a stable state within the body's environment (e.g, in dysfunctional macrophage cells). Nanoplatforms may also be designed to closely monitor the chemistry of nanostructures through which, nanomaterials may disintegrate into their specific building fragments, which are not expected to be hazardous following drug transmission 116 .

Nanostructure as a therapeutic substance

Photodynamic treatment.

Photodynamic therapy (PDT) across cancer services has increasingly become a powerful therapeutic alternative. PDT uses a photosensitizer that is recognized as a light-activating molecule that absorbs light from certain wavelengths in order to produce molecular species that are dependent on cytotoxic oxygen. Such sensitive chemical species are responsible for the destruction of subcellular organelles and also cell membranes, which consequently induce apoptosis, necrosis, or autophagia, in other words, cell death 117 . The energy obtained from light can lead to free oxygen radicals' production from superoxide, hydrogen peroxide, and hydroxyl radicals with molecular oxygen 118 . The efficacy of PDT depends to a large extent on the degree to which photosensitizers can induce singlet oxygen generation, as well as on their ability to deliver it specifically to the target tumor tissue at therapeutic concentrations. Since single oxygen-based products have a limited lifespan of fewer than 3.5 microseconds and can only be distributed between 0.01 and 0.02 lm, their degree of disruption or damage is limited to the concentration of photosensitizing substances typically found in the endoplasmic reticulum or mitochondria 119 . Since some photosensitizers capture light below 700 nm across the visible spectrum, light penetration is minimized to only a few millimeters, allowing only relatively superficial lesions to be treated 120 . However, developments in optical engineering have made it possible to create optical fibers that can be inserted into endoscopes, bronchoscopes, and colonoscopes in order to facilitate the transmission of light to the inner body cavities, thus increasing the range of PDT 121 . PDT is currently being studied in the treatment of many tumors such as bladder, skin, lung, prostate, pancreatic, esophageal, and stomach tumors 122 , 123 .

It is theoretically possible to identify the nanostructures used in PDT as active or passive 124 . PDT nanomaterials in a passive manner photosensitize vectors and can be manufactured either from environmentally friendly or non-polymeric components like ceramic and metal nanostructures 125 .

Due to their potential to include large carrier photosensitizers, it has been demonstrated that biodegradable nanostructure containers consisting of PLA or PLGA are a substitute for liposomes 126 . This is critical as photosensitizers with inherently low water solubility are highly hydrophobic and culminate in the solution aggregation that reduces the possibility to control them. The morphological features of the polymeric matrix may also be ideal for the controlled deterioration of the polymer content and therefore good for triggering the release of the photosensitizer compound 127 . Photosensitizer-loaded nanomaterials have been shown to have more photoactivity than "free" photosensitizers 128 . In addition, due to their increased level of intracellular absorption through endocytosis, smaller nanocarriers have significantly higher phototoxic effects compared to relatively large nanovectors, triggering the release of photosensitizers inside the cytoplasm but not in the extracellular environment 117 . Moreover, the narrower the scale of the nanostructure is, the higher the surface-to-volume ratio will be which increases the surface area that is accessible to the ambient environment, leading to higher levels of photosensitizer release 129 . Photosensitizers may be filled with non-biodegradable and non-compostable substances and may also be more beneficial to be filled with organic polymer-based nanostructures regarding better durability; regulation of pore size, volume, pH tolerance, and mitigating microbial hazards. In addition, specific targeting of tumor tissue may be quickly achieved, allowing accurate agglomeration across the cancer target of photosensitizers, thus reducing the concentration of photosensitizers throughout healthy non-target body tissues. This will therefore reduce any amount of light-sensitive substances required to produce a comparable optical toxicity effect and thus increase the capacity of phototherapy. Low irradiance can be utalized to convert the significantly higher emission energy by employing two-photon absorbing dyes, so that single-oxygen radicals can be directly generated from the oxygen-driven molecule. The benefit of the entire mechanism is that light beam is allowed into deeper tissues within a clear tissue gap (from 750 to 1000 nm). However, the toxicity of the dye remains a major concern. The dye entrapment into a biologically inert nanomaterial container will also help reduce its toxic effect on healthy tissues, allowing PDT to penetrate deeper body tissues and organs. Several other researchers have also investigated the potential use of light-sensitive substances with exciting properties (receptors capable of having energy) that gain fluorescence resonance energy from photon-absorbing dyes called energy donors 130 . This method provides an effective energy transfer between the intermediate dye and the activated encapsulated photosensitizer through the physical embodiment of the dye as well as the photosensitizer within the same nanostructure. In this method, the load-bearing strength of the dyes capable of absorbing photons must be significantly greater than those photosensitizers capable of accepting energy for a successful photon excitation. Since functionalized silica nanomaterials are biocompatible, durable with no releasing embedded hydrophobic compounds and ideal for PDT, they have therefore gained importance as their porous framework becomes permeable to oxygen molecules 131 , 132 .

Without a photosensitizer, active PDT nanostructures can produce free radicals and reactive species themselves. This was initially understood by Samia et al, who discovered that the semiconductor QDs were capable of producing singlet oxygen individually using the transfer of energy from the triplet state without photosensitive materials despite a poorer specification, to have access to photosensitive substances through the transfer of fluorescence-based resonance energy 133 In order to contribute to the enclosure of photosensitive substances and directing these substances towards cancer cells, other researchers have shown the potential of nanomaterials to play an extremely effective intermediate role through the PDT method 134 . During radiation with x-rays, such nanostructures can release luminance with an adequate wavelength to functionalize photosensitizers, bringing treatment to locations deep inside a tissue that is usually hardly exposed to radiation. Comparatively, converting nanostructures appears to be effective for absorbing low-energy radioactivity (e.g. NIR irradiance that is capable to penetrate body tissues of approximately a magnitude greater than light waves) or generating more energy-intensive radiance that can also trigger photosensitive substances to generate reactive single oxygen species across the microenvironment 135 , 136 . This is achieved after 2 low-energy photons are captured at the same time, causing nanostructures to move from the basement to the exciting stage using transformation metals or rare-earth ions such as lanthanide. Quantum conversion occurs mechanically, after absorption of the first photon, through a simulated intermediate phase 137 , 138 .

Silencing the gene

Antisense oligonucleotides, plasmid DNA, or small interference RNA (siRNA) are core tools in gene therapy, which is described as a minimum dose gene control 139 . Dicer, i.e. ribonuclease (RNase III endonuclease), forms the siRNA cleavage ability and the clearance of double-stranded RNA. siRNAs are small pieces of double-stranded RNA ranging in length from 20 to 25 nucleotides. In addition to their nucleotide sequence, they can interfere with the translation of unique mRNAs 140 . siRNAs come into contact with a multipurpose protein called Argonaut, the catalytic portion of the mixture of the silencing structure triggered by the RNA 141 . Double siRNA is unscrewed, and Argonaut retards the traveler's RNA strand, allowing the additional mRNA to attach to the residual or anti-sense strand 142 . Subsequently, through its endonuclease operation, Argonaut splits the mRNA, which contributes to the silencing of the expression of the gene, better recognized as RNAi (RNA interference) 143 . This influence may keep on for 3 to 7 days in rapidly dividing cells or for several weeks within cells without dividing properties.

Many molecular targets have been identified to be manipulated in well-characterized pathways that cause cancer. SiRNA, therefore, offers a great deal of optimism that would be sufficient to inhibit not only one gene but so many genomes that contribute to the strong potency of tumor progression and enable several mechanisms to be targeted simultaneously. Positive findings from many in vivo and in vitro RNAi investigations have been obtained in cancer-related mechanisms, such as cell cycle control, tumor-host interactions, and cell senescence 144 . However, many drawbacks are shown by Miele et al, which further limit the efficacy of siRNA in therapy, such as A) transmission difficulties, B) adverse consequences associated with non-objective activities (i.e. a sectional combination of siRNA with a complementary sequence of unintentional mRNA transcription factors) and C) disruption of the cellular machinery of physiological roles 145 .

As released into the circulatory system, unfunctionalized siRNA compounds are extremely reactive and described as limited half-life attributed to serum A-type RNase nucleases and accelerated renal removal. In addition, due to the massive and intense charges of polyanions on the backbone of the phosphate group, non-functional siRNA complexes are unlikely to penetrate the cells, leading to electrostatic repulsive forces from large negative anion charges on the outer surface of the cell membrane. Although it has been shown that chemical functionalization of siRNA enhances intravascular stability and restricts the body's innate immune response without serious impairment of RNAi function, alternative patterns of diffusion involved with nanomaterials, have recently been explored to find additional forms of safe transfer of siRNA 146 , 147 . Nanostructures provide a highly specific surface area and therefore have a large exterior surface compared to their small dimensions for transporting siRNA. Nanostructures can preserve and secure siRNA during intravenous infusion 148 . This contributes to the specific targeted and packed delivery of siRNA to cancer cells after surface modification with tissue-specific ligands.

Nanomaterials are effectively absorbed into the cells, typically through receptor-mediated endocytosis also known as membrane fusion 149 . While inside the target cells, they reach the intracellular transport system, through which the siRNA must be limited until the lysosomal system reduces the RNA 150 . Some of the molecular tools which are used to enhance endosomal evasion include fusogenic proteins and lipids, pH-sensitive polyplexes/lipoplexes, and photosensitive compounds 151 .

Nanoliposomes are potentially the nearest clinical definition of all siRNA-nanoparticle delivery strategies being developed. Nanoliposomes were primarily constructed from organic matter comprised of a phospholipid bilayer and an aqueous center capable of binding to the siRNA. This is achieved by employing electrostatic interactions-stabilized frameworks 152 , 153 . They are usually inert in charge and about 30 to 40 nm in diameter, allowing the cells to absorb them effectively. Nanoliposomes protect siRNA from endonuclease in the bloodstream although their limited serum half-life and rapid RES (e.g. lung, liver, bone marrow, and spleen) inhibit their use for therapy and require repeated injection 154 . Many groups are already studying the future use of sustained-release polymer mixtures to address this issue 155 , 156 . As they are made from physiological lipids, stable lipid nanostructures are being increasingly studied showing considerable bioavailability and limited biological toxic effects. non-biological synthetic nanostructures, including noble metals and inorganic crystalline structures, have also been investigated as vectors for gene transmission as a result of their improved durability and convenient oligonucleotide functionality 81 , 157 , 158 . The optimum diameter of synthetic nanomaterial transporters tends to be between 5 and 100 nm. Due to accelerated renal removal, nanomaterials are designed to measure less than 5 nm, while those larger than 100 nm are captured by RES (where activated monocytes and macrophages degrade these nanomaterial transporters) 159 . Besides, the add-on mechanism allows particles more than 200 nm to be removed easier than narrower nanostructures. Oishi et al first achieved the integration of siRNA into gold nanomaterials using a layer-by-layer assembly process model to design macromolecular configurations to facilitate the continuous release and delivery of siRNA. Also, new porous-silicon delivery approaches are being implemented as the chemical modulation of both the vehicle surface and the transported medicine is needed 160 .

Another first experimental study was carried out by Davis et al in 2010, in which siRNA was packed into a nanostructure consisting of a linear polymer, based on cyclodextrin (a human transferrin-based protein that enables cancerous cells with surface transferrin receptors), as well as a PEG (that facilitates nanomaterial durability to minimize the expression of the M2 subunit of ribonucleotide reductase). Throughout their clinical development, siRNA-packed and ribonucleotide reductase-targeted nanomaterials were routinely delivered to melanoma-bearing patients who were highly resistant to primary therapy. Patients were treated every 21 days on days 10, 8, 3, and 1 with 30 minutes of intravenous infusion. In a small number of post-treatment patients, tumor biopsies revealed the nanomaterials inside the cytoplasmic compartment with subsequent decreases in both protein levels and mRNA expression of the M2 subunit of ribonucleotide reductase, indicating that systemic delivery of siRNA to humans may generate specific gene suppression through the RNAi process. Little, however, has been understood concerning the pharmacodynamics of the RNAi result which depends on the mixture period of the disassembly of the nanostructure and also on the time the siRNA remains inside the RNAi machinery. The use of siRNA against persistent myeloid leukemia, liver cancer, advanced solid tumors, and neuroblastoma is also being studied in many other early-stage medical investigations 161 .

Photothermal treatment

The application of nanomaterials in combination with heat opens a new window toward the effective treatment of malignant tissues. Hyperthermia is referred to temperatures between 40 and 45°C. In addition to apoptosis, temperatures above 42°C have been shown to cause cancer cells more sensitive to subsequent therapies, such as radiation, while temperatures above 45°C are capable of causing direct tumor cell death (e.g. thermoablation) 162 . Tumor-related hyperthermal therapy involves applying thermal energy to tumors using microwaves, radiofrequency (RF), ultrasound, or magnetic fields to cause irreparable cellular injury through membrane softening/loosing and protein denaturation, eventually leading to fatal tumor cell injury 163 . As this actual impact is much more specific to malignant tissues due to their decreased thermal resistance, thermal therapy is questioned because of injury to the nearby healthy tissue. Photothermal therapy (PTT) seeks to resolve this problem by using photothermal substances to achieve more regulated and specific warming in its target region, thereby limiting thermal destruction throughout the tumor 164 .

We need to provide an improved absorption ratio of light as well as efficient light-to-heat conversion rates for photothermal agents to be advantageous. Natural chromophores that struggle with poor absorption or exogenous colors (e.g. green indocyanine) and are affected by photobleaching are conventional agents 165 . Even so, these troubles have been resolved by the advancement of noble metallic nanostructures (e.g. nanotubes of gold nanospheres, nanotubes, and nanotubes) and carbon nanotubes because they have high absorption in NIR electromagnetic spectrum areas, particularly around 650 to 900 nanometres, due to plasmon surface resonance (SPR) 166 , 167 . It is beneficial because, in this range, the majority of biological tissues exhibit limited absorption of light, making the light easier to penetrate in depth. In general, spherical gold nanostructures have the maximum absorption of SPR throughout the visible portion of the spectrum of approximately 520 nanometres 168 . Gold nanotubes, on the other hand, have two absorbance frequency bands in the trajectory of each rod shape (e.g. longitudinal and transverse axes), with a high peak intensity of almost 520 nm in the transverse plasmon band, as well as a high-frequency longitudinal plasmon band, which can be adjusted across the NIR area on the basis of their length-to-width proportion. this makes these nanotubes appealing for in vivo investigations. In comparison, the maximum SPR absorbance for nanoshells based on the gold element can be adjusted by changing the radius ratio of the thickness-to-core proportion of the shell. Their absorbance ratio is 4 to 5 times higher than that provided by photothermal agents due to the SPR of nanostructures 169 .

Photo-excitation of light-frequency metallic nanomaterials in parallel with the SPR-related absorption band of the nanostructure lead to electron-based gas development, which heats up and generates thermal energy but quickly cools by exchanging energies with the nanostructure crystal structure in about 1 picosecond (ps) 170 . After almost 100 ps s , the crystal structure itself cools by exchanging heat with the surrounding media to induce regional tissue destruction. The heating of gold nanostructures often induces a cavitation bubble around the nanostructure. Actually, the heat-triggered cell breakdown processes mentioned above, in turn, lead to mechanical stress that contributes to long-term cell damage 171 . Surveys have shown that, compared to traditional dyes, nanostructures typically improve light-to-heat transfer, requiring less laser energy to achieve localized cell destruction 172 . Nanomaterials need to be tens to hundreds of nanometers in diameter to improve the efficiency of light-to-heat conversion, but this contributes to their low absorption and aggregation within the RES 173 . Researchers are therefore particularly interested in the application of tiny noble metallic nanostructures which, by self-assembly, escape the RES but accumulate at the tumor site. Loading nanoparticles to tumor cells would improve optical density, resulting in extremely low laser power required to increase the temperature above the threshold of cell destruction 174 . Initially, photosensitizer nanostructures must be concentrated inside the targeted tumor after their intravenous/local administration intended to have effective PTT. This can be achieved by surface modification of nanostructures with specific substances capable of targeting the tumor. Cell culture experiments, for example, have recently shown that gold nanostructures conjugated with anti-epidermal growth factor receptor (anti-EGFR) antibody can directly attach or charge carcinogenic cells representing EGFR to allow PTT to produce high temperature shocks of around 70 °C to 80 °C and consequently, contribute to thermal ablation necrosis of tumors 175 , 176 . By comparison, for cell types that did not have nanomaterial tags, no photothermal destruction was reported while cell death occurred for four times that the thermal energy required for the destruction of cancer cells was provided by gold nanomaterials labeled anti-EGFR. The next step is to transmit light radiation directly to the tumor region, which is typically achieved by using NIR-based laser instruments, eithine fiber optic catheters and endoscopes capable of being mounted close to the tumor. The promising effects of PTT on cultured cells, ex vivo human samples and live experimental animals have shown significant potential for this cancer treatment strategy, either independently or in conjunction with many other therapeutic approaches. Initial clinical experiments with AuroShell nanostructures consisting of a metallic shell of gold and a non-conductive dielectric core are launched for advanced head and neck cancers using NIR-PTT 177 .

Iron oxide nanomaterials within water have also been found to produce thermal energy in presence of an endogenic alternating magnetic field when introduced into tumors 178 . Iron nanostructures provide a high particulate density inside the water (e.g. magnetic fluids), which is responsible for making a large overall outer surface area of the magnetic components, resulting in a remarkable strength of their absorption properties. This makes them a particularly useful tool to reach the uncontacted tumor intracellular environment 179 . Magnetic fluid hyperthermia, on the other hand, has shown positive outcomes for malignant glioma, prostate cancer, and breast cancer (phase 1 clinical trials are currently underway for prostate cancer and phase 2 clinical trials for cerebral tumors) 180 . Hyperthermia based on magnetic fluid, however, cannot currently be achieved by the systematic administration of nanostructures of iron oxides.

Nanostructures as carriers for image processing

Standardized image processing technology employing magnetic resonance imaging (MRI), simple radiographs, computed tomography (CT), and ultrasound are commonly utilized for both cancer-related monitoring and subsequent intervention 181 . Such techniques, however, depend on the detection of cancer until they represent a recognizable activity at about 1 cm, where the tumor volume is already close to 1 billion cancer cells. Conceptual changes have also taken place over the last few years, from anatomical image processing, which recognizes macroscopic/gross pathology, to molecular diagnostic images, which facilitate the diagnosis of cancer on a molecular scale even before phenotypic shifts occur 182 . Molecular diagnosis enables the in vivo characterization of the genetic alterations that occur in oncogenesis, thus determining the method of molecular treatment highly advantageous to the patient population (e.g. personalized medicine) 183 , 184 . It also facilitates continuous non-destructive monitoring of the response, development, and transformation of the condition during treatment or relapse. Conventional imaging techniques have the potential to use imaging compounds to demonstrate current characteristics, (e.g. blood vessels and tissue perfusion after intravenous injection of a contrast agent). Tiny molecules of approximately 2,000 daltons or 1 nm were conventionally used as imaging factors (e.g. iodinated small molecules for CT, 2-deoxy-2-(18F)fluoro-D-glucose (FDG) for positron emission tomography (PET), and chelated gadolinium for MRI) in clinical settings 185 , 186 . However, the development of modern probes resulted in poor signal strength, weak durability, non-specificity, and accelerated removal from the circulatory system. By addressing these drawbacks, nanostructures have shown considerable potential and are therefore actively used as molecular diagnostics. Nanostructures, for example, can improve signal strength when using optical imaging techniques, allowing lower cellular communities to be visualized at higher tissue depths, and also producing imaging signatures that are persistent over long periods 187 .

Since nanoparticles can be covered with several types of ligands, they also have strong affinity and specificity that allow for binding interactions with target cell groups that increase their persistent affiliation by 4 to 5 magnitude orders 188 . It is beneficial since more nanostructures are concentrated at the precise location of the tumor, thus increasing the signal-to-noise ratio and making it easier to properly illuminate cancerous tissues compared to the nearby healthy tissue. The bulk of nano-sized imaging substances are often greater than 10 nm and are therefore not normally removed from the circulatory system by the kidneys; this assists them to have prolonged circulation periods relative to smaller particles (i.e. minutes vs. days) 31 , 189 . This is beneficial as it facilitates repetitive image analysis without the need for more nanoparticles to be administered.

Experiments have also shown that narrower nanostructures have more homogeneous tissue bio-distribution compared to spherical nanomaterials and non-spherical nanomaterials (e.g. nanotubes, nanodisks, nanoworms, etc.) being more effectively distributed to target tissues 190 . In addition, they must be balanced against unexpected non-sphere-related toxic effects. Because cancer is rarely detected by a single molecular-based approach, the sensitivity of clinical diagnosis can be improved by identifying several molecular targets that are up-regulated while oncogenesis is present (e.g., a process known as multiplexing) 191 , 192 . One way to do this is to label multiple nanomaterials, each against a specific aspect of a molecular biomarker, and then deliver all of these nanomaterials simultaneously 193 . Signals identified from multiple nanomaterials attached to cancer cells can then be decoded to allow therapists to evaluate the molecular fingerprint of tumors. This would make it possible, in particular, for the patient to be provided with scheduled molecularly targeted treatment. If the molecular signature of the cancer is already understood, an alternative approach is to mark a single nanostructure with many separate ligands, each of which to be directed to different molecular targets and recognized as over-regulated in tumors under examination 194 . Compared to the background tissue, the tumor may have many of these targets thus, more nanomaterials can be attached and bring a larger signal. Nanostructures can eventually be constructed to be multidimensional so that two or more separate imaging techniques (e.g. MRI and fluorescence) can be applied for visualization of the tumor 195 . Several researchers are also actively exploring strategies for the separate administration of sub-components of nanostructures to improve the efficiency of the transmission of nano-sized imaging substances to the location of the tumor mass. Such subcomponents can also be self-assembled in presence of stimuli, such as pH fall, adaptation, or enzyme cleavage, to create a supramolecular nanostructure probe that can eventually be used for image processing 196 - 198 . The value of this technique is that these specific sub-components are narrower and more penetrative to the tumor to confirm aggregation only at the specified location. An example can be monomers (containing gadolinium bind 2-cyanobenzothiazole and 1,2-aminothiole) and protease-sensitive motive probes(like caspase-3 and furin,) that are over-expressed across tumor cells 199 .

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently used in wide medical applications including cardiovascular disease, hepatic injury, lymphatic system, and cell imaging. Still, several pre-clinical investigations are already underway to develop different nanoscale therapies 200 , 201 . Iron oxide (maghemite, Fe 2 O 3 ; magnetite, Fe 3 O 4 ) nanomaterials, if their central dimension is 20 nm and smaller, become superparamagnetic at the ambient temperature, allowing around micromolar levels to adjust T 2 relaxation periods and water-related protons to improve the contrast in MRI images 202 . In vivo , SPIONs are often known to have minimal toxic effects as they are assumed to be environmentally friendly; With nanomaterial iron breakdown and its further release into the normal plasma iron stream, it will eventually become integrated into erythrocyte hemoglobin and used for other metabolic pathways 203 , 204 . Although SPIONs are phagocytized by RES cells, they have been used to diagnose liver lesions. Since healthy liver parenchyma produces RES, SPIONs may accumulate and weaken the signal strength for both T 1 and T 2 photos. Many liver tumors, on the other hand, restrict producing RES and therefore refuse to absorb SPIONs that increase the differentiated contrast between the mass of the tumor (large signal pulses) and the adjacent tissue (poor signal pattern) 205 . Furthermore, since SPIONs are paired with ligands for successful targeting, these signal properties are reversed. SPIONs can now be collected at the location of the tumor under these conditions, resulting in weak signaling relative to baseline liver parenchyma; this also depends on SPIONs that restrict RES 206 . Polymeric materials typically SPIONs are used in targeted delivery to inhibit RES and promote colloidal durability and cytocompatibility (i.e., starch, dextran, or PEG) 40 , 207 . As a result, ligand molecules like folate are grafted onto SPIONs by their polymer coating materials,(either PEG or dextran) 208 . Folate is used as a ligand molecule because folate receptors are usually up-regulated/highly expressed on the apical surface of cells during the cell proliferation of malignant tumors due to the essential role of folate in cancer while these receptors are present on the outer surface of epithelial cells in limited quantities. 209 . Transferrin molecule also strongly bounds to SPIONs when attached to the transferrin receptor (generally referred to as CD71), a type II transmembrane glycoprotein that is differentiated and highly expressed across the proliferating surfaces of cancer cells due to its elevated iron requirements 209 , 210 . SPIONs have also been integrated into different sequences of peptides, including arginylglycyl-aspartic acid (RGD), and may combine with integrins such as avb3 expressed on proliferating endothelial plasma membranes (including those experiencing angiogenesis) 211 . Initially, the diagnosis of disease in vivo was not looking feasible by SPIONs functionalized with monoclonal antibodies due to the large particulate diameter that allowed its accelerated removal by RES. Even so, with some experiments suggesting monoclonal antibody-conjugated SPIONs have a high affinity to antigen-expressing tissues, this has proved not to be the case 212 . In laboratory animals, EGFR antibodies were integrated with SPIONs to detect small lung cells, esophageal squamous cells, and colorectal carcinomas 213 - 217 . However, it dramatically enhanced the scale of the nanoparticle-antibody conjugation system, and a decrease in stealth-like functionality was observed. Some classes are “ already grafted SPIONs to aptamers ”, which are synthetic rather small selected sequences of oligonucleotides that can bind to ligands with extreme affinity and specificity. Double-modality probes such as dextran-coated 64 Cu-SPIONs are now being produced, while clinicians are planning to implement them for dual-mode MRI/PET image processing in the immediate future. Throughout clinical settings, optical imaging has never achieved its maximum capacity and, in most cases, appears to be a preclinical/research imaging technique 218 .

Fluorescent has traditionally been used for optical imaging. In vivo uses of fluorescence are restricted by 1) the minimal amount of fluorescent-based imaging substances accessible only throughout the NIR range, thus preventing the use of low-power laser beams for sampling; 2) the potential background autofluorescence in superficial body tissues, thus limiting the depth or intensity of such imaging; 3) broad spectrum overlap between fluorescent-based imaging substances, preventing different targets from being detected at the same time; and 4) accelerated photobleaching of fluorescent-based substances that limits the length of the investigation 218 - 220 .

QDs, as a modern type of nanomaterials, are used for optical image analysis. An example is nanocrystalline semiconductor materials, usually made of metallic materials such as zinc or cadmium from sulfides or selenides, which vary in diameter between 2 and 10 nanometers 221 - 223 . The wavelength ranges of the radiation generated do not depend on the QD components, but rather on the structural aspects of the QDs. Thus, the ability to track or adjust the QD dimension properly determines the wavelength, and the coloring of the reflected light. The latter is commonly referred to as the "size quantization effect" 224 . Regarding the interpretation of the light emitted through human beings, the emission pattern of the QD can therefore be configured purposed to provide peaks corresponding to the wavelength range right across the continuum of light waves, regardless of the frequency of excitation. QDs are therefore found to be approximately 20-fold brighter as well as 100-fold more durable than conventional fluorescent reporters (e.g. less sensitive to photobleaching), allowing them to also provide better tissue penetration while becoming more functional for lengthy image processing. QDs are included in a wide range of applications in biological sciences at the molecular level to date. This involves DNA recognition, cell sorting, cell monitoring, and targeting of biological markers through in vivo studies 225 , 226 . QDs have also been conjugated with many bio-based ligands, mainly including EGFR, prostate-specific membrane antigen, RGD, and folate peptides 227 . Multimodality QDs are already being produced including QDs labeled with RDG peptides for dual-modality fluorescence imaging, based on both PET and near-infrared (NIRF) 228 . The NIRF signal enables increased penetration of the tissue by fluorescence emissions outside the spectral range of the bloodstream or tissue (e.g. autofluorescence) resulting in increased signal-to-background noise coefficients. The PET signal pattern provides an extremely detailed analysis of the tomographic image 229 .

In addition, a further method of optical imaging recognized as Raman spectroscopy has shown considerable advantages in overcoming several fluorescence deficiencies 230 . Raman spectroscopy relies on inelastic light scattering compared to fluorescence, where light absorption occurs. If monochromatic light directly impacts a molecule, (typically through a laser beam, across the near-ultraviolet, NIR, or visible spectrum) any photon may become dispersed. 231 . A Part of the incident photon energy will also be transferred to the molecule, allowing it to oscillate further and contribute to less energy becoming inelastically dispersed by the photon. The "Raman effect" is defined as the exchange of energy between the incident light and the scattering molecule. Because the intensity of the Raman effect is fundamentally poor (about 1 photon is distributed inelastically across all elastically dispersed photons), this restricts the susceptibility and therefore the medicinal implementation of the Raman spectroscopy 232 . Advances across nanoscience have made it possible to synthesize nanomaterials that can solve the problem by reaping the benefits of the surface-enhanced Raman scattering (SERS) effect 233 . SERS is a plasmon-based phenomenon in which an important improvement in the occurrence of an electromagnetic field is observed using adsorbed substances based on noble metals with roughened nano-scale shapes on the surface, which contributes to greater Raman signals. These nanostructures have therefore been developed, containing a roughened center of gold in the range of 60 nanometres, which is covered by a single-layer "Raman organic molecule" with a silica shell in the range of 30 nanometres. The generated field based on electromagnetic associations of the SERS-based organic molecule layer is therefore remarkably enhanced which greatly improves the amplitude of the Raman signal. This enables the identification of nanomaterials across deeper tissues at picomolar concentrations making it a suitable in vivo imaging tool. Each nanomaterial may have its spectral fingerprint. As the organic molecule of Raman alters, it allows several nanomaterials to be observed in vivo at the same time by multiplexing them 234 . This is due to the different chemical bonds of each active layer of Raman, which lead to different molecular-based fluctuations following the excitation of the laser beam. This ends up with a unique signal for each molecule in their Raman signal patterns (Figure ​ (Figure6). 6 ). The latest investigation has shown that nearly 5 spectroscopic fingerprints of biological systems can be detected simultaneously. Therefore, when a specific fingerprint is correlated with a specific nanostructure-bound targeting ligand (e.g. monoclonal antibody, peptide, aptamer, or affibody), cancer molecular profiling can be calculated by spectral analysis of the Raman fingerprints from the tumor. A novel triple modal nanomaterial based on MRI and photoacoustic Raman image processing has recently been produced to facilitate resection and also recognition of brain tumors 234 . Nanostructures enable: 1) full brain tumor placing through MRI using gadolinium covered particles intraoperative and preoperative macroscopic delineation; 2) increased spatial resolution during three-dimensional scanning through its gold center using photoacoustic image analysis; and finally 3) excellent specificity, extremely good resolution, and excellent surface sensitivity through Raman for imaging. Although the possible implementation of SERS and QDs nanomaterials, is proved to be considerable, until we can see their use in conventional clinical settings, concerns about their hazardous toxic properties (in particular the cadmium product) would have to be addressed initially.

A graphic illustration of a nanostructure, based on Raman. Raman nanostructures produce a Raman signal/spectral trace after activation and/or stimulation of the Raman molecular layer: (A) Raman nanostructures are used for multiplexing images; (B) An example of the spectroscopic strength map of the Raman-based nanostructure with SERS effect and ability of tumor targeting.

Nanomaterials have also been widely produced for photoacoustic-based imaging, a special non-ionizing radiation scanning technique that brings about optical and ultrasound visualization 235 . The stated procedure captures nanosecond pulses of infrared light and converts them to dynamic energy. As well, regionalized thermal energy, during which the nanomaterial further produces a wave of RF can be sensed and converted into an ultrasound-like illustration in real-time.

Optical absorption can be correlated either with internal substances (e.g. hemoglobin) or with externally supplied molecules (e.g. SPIONs, nanoclusters, single-walled carbon nanotubes (SWCNTs), and gold nanoparticles) 236 , 237 . Nanomaterial imaging compounds are shown to generate more photoacoustic signaling than smaller substances based on the mole-to-mole ratio 238 . Although these gold nanomaterials were eventually preferred due to their potent absorbance properties and appropriate for monitoring their absorption spectrum (enabling multiplexing techniques), their comparatively large measure leads to accelerated removal of circulation through the RES 239 . However, laboratory experiments using gold and copper nanomaterials provided encouraging results of photoacoustic imaging while visualizing the lymphovascular axillary invasion of breast cancer to classify sentinel lymph nodes 235 , 240 . Even so, due to their unusually high aspect ratio (roughly 1:100) and large surface area, the advancement of SWCNTs as a photoacoustic image processing operator has become of considerable significance 241 . These characteristics reduce their absorption of RES while they are increasingly preferred for molecular targets due to their multivalence effects. Moreover, RGD peptides have been grafted with SWCNTs and used as contrast media for photoacoustic image analysis of tumor mass in a non-invasive manner 242 .

Nanostructures for the design of therapeutic systems

Multifunctional therapeutic nanostructures in future.

Theranostics define the potential within the material, including nanostructures, to be utilized for detection and therapy simultaneously 243 . The aim is to create intelligent nanostructures that provide diagnostic features, targeted therapy, and track the responsiveness of therapeutic interventions within a single interconnected framework. Medication result is expected to improve through the development of these multifunctional nanostructures, with minimized costs and risks. With the advanced polymerization and emulsifying strategies, the hydrophilic and hydrophobic nanomaterials can now be developed, enabling them to be stored in a variety of functional substances (e.g. hydrophobic therapeutic substances, hydrophobic contrast media, etc.) 91 , 244 , 245 .

Regarding anticancer drug candidates, the SPIONs throughout the MRI are studied comprehensively to be treated externally in combination with individual chemotherapy drugs (e.g. trastuzumab, methotrexate, and temozolomide) including mixed hydrophilic and hydrophobic chemotherapy drugs in a double capsule (e.g. paclitaxel and doxorubicin) 246 . More complicated nanoplatforms are being designed using polymer liposomal lipid-coated and tumor-targeting folate-coated lipid coatings that co-encapsulate SPIONs for image processing. Besides, doxorubicin is used for controlled drug release 247 , 248 . Other structures involve the use of SPION cores by a polycation coating layer on the surface (e.g. polyethylene and poly hexamethylene biguanide) that can attach siRNA to form magnetic vectors by electrostatic interactions. This can easily locate on the outer surface of the target cell by the desired magnetic field intensity 249 . This promotes the absorption of the magnetic vector in the endosomes of the cells, thus maximizing the efficacy of siRNA transfection. SPIONs were also modified in the following ways: radiolabelled with 64Cu (for hybrid PET/MRI image processing), RGD-functionalized (for targeting tumor vasculature), and doxorubicin-conjugated (for cancer treatment). Because PET has an extremely good susceptibility, but a relatively low spatial resolution, its conjuncture with MRI can offer remarkably soft tissue images as well as a contrasting spatial resolution that is advantageous but not ideal for CT 250 . In addition, doxorubicin with pH-sensitive properties has been conjugated to PEGylated SPIONs by hydrazone bonds which allow the drug to be released in a controlled manner to the acidic microenvironment surrounding the tumor 251 . However, these novel SPIONs and several other sophisticated nanostructures have been evaluated through cultured cancer cells and have yet to be confirmed for living organisms. However, these promising outcomes bring plenty of positive prospects for the near future. Within the infrared portion of the high-intensity electromagnetic spectral range (e.g. 700 to 1100 nm) where the biological structures have a transparent window, carbon nanotubes (CNTs) are investigated in both optical and photoacoustic image analyses because they have a good optical absorption coefficient 252 . This makes them suitable for tumor treatment with near-infrared photothermal ablation, with a dose and CNT-dependent increase in temperature of the inside of the indicated tumors. Furthermore, since they can quickly cross biological boundaries, CNTs have been studied for their use in the transmission of genes and drugs 253 . Although the process during which the CNTs are accumulated through cells is still not well understood, they may reach and enter the cells regardless of the cell shape and their functional surface groups, CNTs provide the ability to be mixed with chemotherapy drugs such as paclitaxel, doxorubicin, methotrexate, methotrexate, gemcitabine, and cisplatin due to the potential of their spine to construct supramolecular structures 254 . Some researchers have also used CNTs in anticancer immunotherapy 255 , which utilizes CNTs as antigen-presenting vectors to strengthen tumor-dependent poorly immunogenic peptides/antigens to induce tumor response in the humoral immune system 255 , 256 . Cationic CNTs have also been used for both cultured cells and xenograft mice experiments as molecular carriers for siRNA therapy for the suppression/silence of gene expression 257 , 258 . Gold nanomaterials used for photoacoustic and optical image processing can also be used for PTT 193 , 259 . The elevated density of electrons inside the metal-based crystal structure of gold nanostructures leads to photon energy absorption after irradiation, which in turn allows the crystalline structure (and thus the nanostructure) to heat up. The limited diameter and rapid thermal energy conversion potential of gold nanostructures are advantageous for the specific delivery of thermal energy and the subsequent destruction of cancer cells with adequate light resources, even without destruction in the underlying normal tissue. While the NIR-mediated treatment strategy has promising dimensions 260 , its efficacy is restricted by its penetration depth, making it limited to treating mainly superficial tumors close to 2 or 3 cm deep. Even so, gold nanomaterials have already been shown to be less efficient with short-wavelength RF to generate thermal energy, RF-based ablation is still the main solution to the challenge of treating deep-sealed malignancies 261 . Macroscopic electrodes are commonly used to stimulate ablation in RF therapy that appears to be unpleasant in causing long-term adjacent tissue injury. Thus, the use of microelectrodes will make this treatment less aggressive and even more effective if nanomaterials are localized precisely within the mass of the tumor. Multimodal nanostructures have already been developed, such as those with a super magnetic center for MRI image analysis and those with a gold shell layer for PTT 262 .

Other structures include microcapsules with a gold nanoshell to facilitate the utilization of PTT as well as silica-coated gold nanotubes in PTT for the enhancement of the ultrasound imaging, based on contrast media, while the latter also helps to demonstrate better x-ray amplification, including in vivo x-ray and CT image analysis. All of these nanostructures provide strength for the destruction of malignant cells. Once they have been functionalized, they can facilitate targeted selective anti-cancer treatment that can be constantly monitored. Gold nanomaterials are now being developed to contribute to the transport of PTT-specific drugs and genes (e.g. siRNA, DNA, and RNA) to the location of the tumor. Gold nanostructures can be used to improve the drug's water solubility, biocompatibility, durability, and also target tissues in form of loads of photosensitizing substances. Gold nanomaterials are sometimes combined with highly hydrophobic and inadequately hydrophilic photosensitizers, such as phthalocyanine, to increase their therapeutic efficacy. In addition, gold nanomaterials may be used for double-modality therapy with photosensitizers. An example of the latter is the combination of PTT and photodynamic therapy 263 - 268 .

Conclusions

Several different uses for nanostructures in cancer control have been explained throughout this paper. Their specific characteristics have encouraged physicians to improve the clinical efficacy of their cancer treatment strategy either as individual forms of treatment with nanomaterial (monotherapy) or as an adjunct to current therapy (combined treatment). While some nanostructures have not yet proved to be effective for clinical translation, some innovative nanostructures have been effectively designed that suggest promising novel therapeutic benefits for cancer therapy in the immediate future. In both pharmacological and physicochemical aspects, all recently formed nanomaterials, whether or not they are used as carrier materials, it is important to closely monitor their diffusion scale, homogeneity, and accuracy between production batches. In addition, the load-bearing capacity of nanomaterials, mainly the capacity of their polymer ligands and ligand layers must be calculated (for instance, by applying absorption spectroscopy, electron dispersion spectroscopy, electron-based microscopy, etc.). Compared to their corresponding bulk materials, nanomaterials have been shown to have unique characteristics that significantly improve their in vivo application. This is because their limited scale will influence their forms of endocytosis process, cellular transport, and mechanisms of action. Furthermore, their large surface-to-volume proportion, surface-to-surface excitability, and loading capacity may significantly alter their physicochemical characteristics, leading to unintended side effects and adverse biological activities. Although several researchers have assessed the toxic consequences of given nanomaterials, the results remain highly fragile, which may be partly attributable to the varying sizes, shapes, and chemical compositions of nanostructures, as well as the structure of the human cell population being studied. Therefore, both in cultured cells and in live experimental animals, long-term and short-term assessments of toxic effects would have to be carried out until the FDA approves these nanomaterials for clinical application. Nanotechnology, however, has secured creating innovative methods for diagnosis, management, and cancer follow-up throughout the 21 st century alongside our ongoing efforts to combat cancer and our commitment to identify molecular pathways of cancers to achieve early intervention.

Acknowledgments

Shiraz University of Medical Sciences supplied the financials to this work and the above authors contributed equally.

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Researchers detect a new molecule in space

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New research from the group of MIT Professor Brett McGuire has revealed the presence of a previously unknown molecule in space. The team's open-access paper, “ Rotational Spectrum and First Interstellar Detection of 2-Methoxyethanol Using ALMA Observations of NGC 6334I ,” appears in April 12 issue of The Astrophysical Journal Letters .

Zachary T.P. Fried , a graduate student in the McGuire group and the lead author of the publication, worked to assemble a puzzle comprised of pieces collected from across the globe, extending beyond MIT to France, Florida, Virginia, and Copenhagen, to achieve this exciting discovery. 

“Our group tries to understand what molecules are present in regions of space where stars and solar systems will eventually take shape,” explains Fried. “This allows us to piece together how chemistry evolves alongside the process of star and planet formation. We do this by looking at the rotational spectra of molecules, the unique patterns of light they give off as they tumble end-over-end in space. These patterns are fingerprints (barcodes) for molecules. To detect new molecules in space, we first must have an idea of what molecule we want to look for, then we can record its spectrum in the lab here on Earth, and then finally we look for that spectrum in space using telescopes.”

Searching for molecules in space

The McGuire Group has recently begun to utilize machine learning to suggest good target molecules to search for. In 2023, one of these machine learning models suggested the researchers target a molecule known as 2-methoxyethanol. 

“There are a number of 'methoxy' molecules in space, like dimethyl ether, methoxymethanol, ethyl methyl ether, and methyl formate, but 2-methoxyethanol would be the largest and most complex ever seen,” says Fried. To detect this molecule using radiotelescope observations, the group first needed to measure and analyze its rotational spectrum on Earth. The researchers combined experiments from the University of Lille (Lille, France), the New College of Florida (Sarasota, Florida), and the McGuire lab at MIT to measure this spectrum over a broadband region of frequencies ranging from the microwave to sub-millimeter wave regimes (approximately 8 to 500 gigahertz). 

The data gleaned from these measurements permitted a search for the molecule using Atacama Large Millimeter/submillimeter Array (ALMA) observations toward two separate star-forming regions: NGC 6334I and IRAS 16293-2422B. Members of the McGuire group analyzed these telescope observations alongside researchers at the National Radio Astronomy Observatory (Charlottesville, Virginia) and the University of Copenhagen, Denmark. 

“Ultimately, we observed 25 rotational lines of 2-methoxyethanol that lined up with the molecular signal observed toward NGC 6334I (the barcode matched!), thus resulting in a secure detection of 2-methoxyethanol in this source,” says Fried. “This allowed us to then derive physical parameters of the molecule toward NGC 6334I, such as its abundance and excitation temperature. It also enabled an investigation of the possible chemical formation pathways from known interstellar precursors.”

Looking forward

Molecular discoveries like this one help the researchers to better understand the development of molecular complexity in space during the star formation process. 2-methoxyethanol, which contains 13 atoms, is quite large for interstellar standards — as of 2021, only six species larger than 13 atoms were detected outside the solar system , many by McGuire’s group, and all of them existing as ringed structures.  

“Continued observations of large molecules and subsequent derivations of their abundances allows us to advance our knowledge of how efficiently large molecules can form and by which specific reactions they may be produced,” says Fried. “Additionally, since we detected this molecule in NGC 6334I but not in IRAS 16293-2422B, we were presented with a unique opportunity to look into how the differing physical conditions of these two sources may be affecting the chemistry that can occur.”

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INFORMS Open Forum

2025 m&som practice-based research competition, 1.  2025 m&som practice-based research competition.

The 2025 M&SOM Practice-Based Research Competition:

A Biennial Practice-Based Paper Competition for the M&SOM Journal

The objectives of the M&SOM Practice-Based Research Competition are to motivate, help develop, reward and highlight high-quality OM research papers with significant practical relevance, and to publish these papers in the M&SOM Journal. This paper competition is distinguished by the following features: (i) its focus on practical impact; (ii) papers considered are not yet published; (iii) involvement of high-level practitioners to evaluate papers; (iv) presentations at the MSOM conference by contestants; (v) organization primarily by the M&SOM journal as opposed to the MSOM Society.

Scope and Admissibility

This competition seeks to reward unpublished OM research papers with a high potential or realized impact on practice. Work not implemented yet may be considered, as long as potential benefits to practice can be ascertained with a high level of confidence. More generally, validity (i.e., the extent to which the results presented do or would apply in practice) is a key evaluation criteria.

All required submission material must be submitted through manuscript central by September 16, 2024 (please select "Practice-Based Research Competition" for the manuscript type) and include:

• An unpublished paper complying with all existing M&SOM journal requirements;
• Additional evidence of potential or realized practical impact, including at a minimum one (possibly confidential) supporting letter by a practitioner who is not a paper co-author;
• A commitment by authors to attempt any requested revision work in good faith and publish their submitted papers in the M&SOM journal if invited to do so by the Academic Competition Committee (see Process section below). This commitment may be stated in a cover letter signed by all paper co-authors.

The main evaluation criteria include the following:

• Extent and validity of the realized or potential practical impact claimed;
• Academic contributions;
• Quality of exposition, including clarity of contributions;
• P otential for academic impact and future related work.

Papers having a substantial overlap with another paper that is already published, accepted or currently under review with another journal are not eligible. Suitable papers already under review with the M&SOM Journal may be considered at any stage of the competition (see Process section below), provided any missing required material is provided by the authors and consent is given by the paper authors, the Department Editor currently overseeing the review and the Competition Chair.

The competition is supported by an Academic Competition Committee working within the Practice department of the journal: it is composed of M&SOM Journal Editorial Board members and chaired by a Competition Chair appointed by the journal EIC. The Competition Chair may appoint individuals to serve as guest Associate Editors for the competition, in consultation with the journal EIC. The competition also involves a Judge Panel composed of high-profile practitioners. The competition selection stages are as follows:

·        In the first review stage, the Academic Competition Committee decides if each submitted paper has enough potential to eventually become an acceptable M&SOM publication within the imposed timeframe, and develops some feedback on the paper. This involves an initial desk review, possibly followed by a subsequent review by a committee member serving as AE and input by 1 or 2 referee(s). Considering all available input, the Competition Chair decides whether or not to invite the authors to submit a revision by a specified deadline for consideration in the second stage;

·        In the second stage (Finalist selection), assigned AEs review submitted revisions, possibly soliciting further input from referee(s), and the Academic Competition Committee considers their input to decide whether each paper should be selected as a Finalist for the competition, which entails acceptance for publication in the journal, possibly conditional on the completion of some revision work;

·        The final stage (prize awards) involves a Judge Panel composed of the Competition Chair and several high-profile practitioners. The Competition Chair appoints the Judges in consultation with the journal EIC, and coordinates their work. The Judges receive the latest paper version and any other submission material in advance, and also consider an oral presentation of each Finalist paper by their author(s) organized at the MSOM Conference. After reviewing the Finalist presentations (perhaps by video if a judge cannot attend), the Judge Panel meets to (i) decide upon the award of one or several First and Second Prizes further distinguishing papers among the Finalists; and (ii) develop written comments/quotes on the work presented to be subsequently used by the Journal, the Society and/or any other parties interested in the promotion of the Finalist papers (e.g., author(s), letter writers, promotion committees, etc.);

·        After revisions are performed by the authors if required, Finalist and prize-winning papers are published in the Journal with a special mention on the paper cover page highlighting their participation and final status in the competition;

·        At every key selection stage described above, the Competition Chair may decide to transfer a rejected paper and any related feedback developed as part of the competition to the EIC for further consideration as part of the Journal's regular submission review process for publication, provided consent is given by the author(s).

2024/2025 Competition Timeline

·        September 16, 2024: Deadline for submission of papers and supporting material;

·        September-November 2024: First round review process;

·        December 2024-January 2025: Academic Competition Committee decides first round outcomes;

·        April 2025: Deadline for selected authors to submit second round paper revisions;

·        May-June 2025: Second round review process, Academic Competition Committee selects Finalist papers;

·        June 28 2025: Finalist presentations and results announcement at the 2025 MSOM Conference (London Business School).

Academic Committee

To be announced.

Judge Panel

Related questions should be sent to Jérémie Gallien (Competition Chair) and Bernadett Racz (Administrative Assistant) at [email protected] and [email protected] .

New Best Answer

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