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Contamination of aquatic food webs with nanomaterials poses a significant ecological and human health challenge. Ingestion of nanomaterials alongside food disrupts digestion and impairs physiological processes, with potential consequences for organism fitness and survival. Complex interactions between nanomaterials and biota further exacerbate the issue, influencing life-history strategies and ecosystem dynamics. Accumulation of nanomaterials within autotrophic and detritus-based food webs raises concerns about biomagnification, especially for top-level consumers and seafood-dependent human populations. Understanding the extent and impact of nanomaterial contamination on aquatic biota is crucial for effective mitigation strategies. To address this challenge, we conducted a comprehensive study evaluating the bioaccumulation effects of graphene oxide (GO), a commonly used nanomaterial, within an aquatic food chain. Using a gnotobiotic freshwater microcosm, we investigated the effects of micro- and nano-scale GO sheets on key organisms: green algae (Chlorella vulgaris), brine shrimp (Artemia salina), and zebrafish (Danio rerio). Two feeding regimes, direct ingestion and trophic transfer, were employed to assess GO uptake and transfer within the food web. Direct exposure involved individual organisms being exposed to either nano- or micro-scale GO sheets, while trophic transfer involved a sequential exposure pathway: algae exposed to GO sheets, artemias feeding on the algae, and zebrafish consuming the artemias. Our study provides critical insights into nanomaterial contamination in aquatic ecosystems. Physicochemical properties of GO sheets, including ζ-potential and dispersion, were influenced by salt culture media, resulting in aggregation under salt conditions. Microscopic imaging confirmed the bioaccumulation of GO sheets within organisms, indicating prolonged exposure and potential long-term effects. Notably, biodistribution analysis in zebrafish demonstrated the penetration of nano-sized GO into the intestinal wall, signifying direct interaction with vital organs. Exposure to GO resulted in increased zebrafish mortality and impaired reproductive performance, particularly through trophic transfer. These findings emphasize the urgent need to address nanomaterial contamination in aquatic food webs to protect ecosystem components and human consumers. Our study highlights the importance of developing effective mitigation strategies to preserve the integrity of aquatic ecosystems, ensure resource sustainability, and safeguard human well-being. In conclusion, our study provides crucial insights into the impact of nanomaterial pollution on aquatic biota. By recognizing the challenges posed by nanomaterial contamination and implementing targeted interventions, we can mitigate the adverse effects, preserving the integrity of aquatic ecosystems and safeguarding human health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A Pb-free FASnI 3 perovskite solar cell improved by using Cu 2 O/ZnO as two-dimensional-based hole/electron transport nanolayers has been proposed and studied by using a SCAPS-1D solar simulator. To calibrate our study, at first, an FTO/ZnO/MAPbI 3 /Cu 2 O/Au multilayer device was simulated, and the numerical results (including a conversion efficiency of 6.06%, an open circuit potential of 0.76 V, a fill factor parameter of 64.91%, and a short circuit electric current density of 12.26 mA/cm 2 ) were compared with the experimental results in the literature. Then, the conversion efficiency of the proposed FASnI 3 -based solar cell was found to improve to 7.83%. The depth profile energy levels, charge carrier concentrations, recombination rate of electron/hole pair, and the FASnI 3 thickness-dependent solar cell efficiency were studied and compared with the results obtained for the MAPbI 3 -containing device (as a benchmark). Interestingly, the FASnI 3 material required to obtain an optimized solar cell is one-half of the material required for an optimized MAPbI 3 -based device, with a thickness of 200 nm. These results indicate that developing more environmentally friendly perovskite solar cells is possible if suitable electron/hole transport layers are selected along with the upcoming Pb-free perovskite absorber layers.

Wound healing is a complex process that often requires intervention to accelerate tissue regeneration and prevent complications. The goal of this research was to assess the potential of bioactive chitosan@poly (ethylene oxide)@CuFe 2 O 4 (CS@PEO@CF) nanofibers for wound healing applications by evaluating their morphology, mechanical properties, and magnetic behavior. Additionally, in vitro and in vivo studies were conducted to investigate their effectiveness in promoting wound healing treatment. The nanoparticles exhibited remarkable antibacterial and antioxidant properties. In the nanofibrous mats, the optimal concentration of CuFe 2 O 4 was determined to be 0.1% Wt/V. Importantly, this concentration did not adversely affect the viability of fibroblast cells, which also identified the ideal concentration. The scaffold's hemocompatibility revealed nonhemolytic properties. Additionally, a wound-healing experiment demonstrated significant migration and growth of fibroblast cells at the edge of the wound. These nanofibrous mats are applied to treat rats with full-thickness excisional wounds. Histopathological analysis of these wounds showed enhanced wound healing ability, as well as regeneration of sebaceous glands and hair follicles within the skin. Overall, the developed wound dressing comprises CuFe 2 O 4 nanoparticles incorporated into CS/PEO nanofibrous mats demonstrating its potential for successful application in wound treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Recently, due to the superior stability and lower risk of toxicity, the development of Pb-free halide double perovskite materials has revived excellent interest. In this work, Pb-free perovskite solar cells (PSCs) with ITO/ETL/Cs 2 AgBiBr 6 /Cu 2 O/Au multilayer structures with Cs 2 AgBiBr 6 double perovskite as the solar light absorber layer, some electron transport layers (ETLs) and Cu 2 O as a hole transport layer have been introduced. Then, the effects of various thicknesses of the absorber layer and also ETL materials, like ZnO, C 60 , CdS, SnO 2 , phenyl-C 61 -butyric acid methyl ester (PCBM), and TiO 2 , on the device performance (including photoelectronic conversion efficiency (PCE), fill factor (FF%), short circuit current density (Jsc), and open-circuit voltage (V OC )) were examined with the help of a solar cell simulator (SCAPS-1D). It is noteworthy that, in the case of all ETL materials, the optimal thickness of the absorber layer was determined to be 400 nm. Then, the maximum PCE values of 20.08%, 17.63%, 14.07%, 12.11%, 14.94%, and 18.83% were obtained for the solar cells containing ZnO, C 60 , CdS, SnO 2 , PCBM, and TiO 2 as the ETL, respectively. These results show that designing/developing Pb-free halide double perovskite devices having comparable PCEs with the Pb-based PSCs is feasible, provided that proper/compatible materials will be used in the multilayer structure of the next generations of solar cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Membranes are ubiquitous tools for modern water treatment technology that critically eliminate hazardous materials such as organic, inorganic, heavy metals, and biomedical pollutants. Nowadays, nano-membranes are of particular interest for myriad applications such as water treatment, desalination, ion exchange, ion concentration control, and several kinds of biomedical applications. However, this state-of-the-art technology suffers from some drawbacks, e.g., toxicity and fouling of contaminants, which makes the synthesis of green and sustainable membranes indeed safety-threatening. Typically, sustainability, non-toxicity, performance optimization, and commercialization are concerns centered on manufacturing green synthesized membranes. Thus, critical issues related to toxicity, biosafety, and mechanistic aspects of green-synthesized nano-membranes have to be systematically and comprehensively reviewed and discussed. Herein we evaluate various aspects of green nano-membranes in terms of their synthesis, characterization, recycling, and commercialization aspects. Nanomaterials intended for nano-membrane development are classified in view of their chemistry/synthesis, advantages, and limitations. Indeed, attaining prominent adsorption capacity and selectivity in green-synthesized nano-membranes requires multi-objective optimization of a number of materials and manufacturing parameters. In addition, the efficacy and removal performance of green nano-membranes are analyzed theoretically and experimentally to provide researchers and manufacturers with a comprehensive image of green nano-membrane efficiency under real environmental conditions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The oxygen-rich organic/inorganic (reduced graphene oxide (rGO)/ZnO 2 -Ag) nanoframeworks as suppliers of O 2 nanobubbles (NBs) with dual pH-and-temperature-sensitive behavior were developed to suppress bacterial growth. It was demonstrated that not only the rate but also the final product of oxygen-rich ZnO 2 decomposition (to an intermediate product of H 2 O 2 ) rate was dramatically controlled by pH adjustment. Furthermore, in the presence of Ag nanoparticles, ̇OH radical generation switched to O 2 NBs evolution by shifting the pH from acidic to basic/neutral conditions, demonstrating an adjustable nanozyme function-ability between catalase and peroxidase-like activity, respectively. Antibacterial properties of the in-situ generated O 2 NBs substantially enhanced against bacterial models including methicillin-resistant Staphylococcus aureus in the presence of rGO. In fact, deflecting the electrons from their main respiratory chain to an oxygen-rich bypath through rGO significantly stimulated reactive oxygen species (ROS) generation, combating bacteria more efficiently. Moreover, NIR laser irradiation-induced temperature rise (due to the inherent photothermal properties of rGO) facilitated ZnO 2 decomposition and accelerated growth and collapse of NBs. The simultaneous microscale thermal and mechanical destructions induced stronger antibacterial behavior. These results hold great promises for designing simple organic/inorganic nanoframeworks as solid sources of NBs with tunable enzyme-like ability in response to environmental conditions suitable for forthcoming graphene-based bio-applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Antimicrobial resistance (AMR) is one of the biggest threats to the environment and health. AMR rapidly invalidates conventional antibiotics, and antimicrobial nanomaterials have been increasingly explored as alternatives. Interestingly, several antimicrobial nanomaterials show AMR-independent antimicrobial effects without detectable new resistance and have therefore been suggested to prevent AMR evolution. In contrast, some are found to trigger the evolution of AMR. Given these seemingly conflicting findings, a timely discussion of the two faces of antimicrobial nanomaterials is urgently needed. This review systematically compares the killing mechanisms and structure-activity relationships of antibiotics and antimicrobial nanomaterials. We then focus on nano-microbe interactions to elucidate the impacts of molecular initiating events on AMR evolution. Finally, we provide an outlook on future antimicrobial nanomaterials and propose design principles for the prevention of AMR evolution., (© 2023 Wiley-VCH GmbH.)

The lead is a heavy metal with hazardous impacts on environment and human life. Lead-free perovskite solar cells have attracted much attention in recent years, due to eco-friendly characteristics. Meanwhile, Pb-containing cells showed the highest efficiencies among the various types of cells. Hence, designing novel Pb-free solar cells with comparable or better performance than the Pb-containing ones is highly required. In this work, a lead-free methyl-ammonium-germanium-iodide (MAGeI 3 )-based perovskite solar cell with ITO/TiO 2 /MAGeI 3 /Spiro-OMeTAD/Ag multilayer nanostructure has been proposed and its main characteristics including open-circuit voltage (V OC ) and power conversion efficiency (η) have been evaluated and compared with those of MAPbI 3 -based cell, in simulation study. The V OC and η of the MAGeI 3 -based cell (1.18 V and 11.9%) have been found comparable with those of the MAPbI 3 one (1.10 V and 14.6%). These results can excite more attention to Ge as a more environment-friendly element than Pb, in highly efficient upcoming perovskite solar cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ultrathin MoS 2 -MoO 3- x heterojunction nanosheets with unique features were introduced as biocompatible, non-cytotoxic, and visible light-sensitive stimulator layers for the controlled differentiation of human neural progenitor cells (hNPCs) into nervous lineages. hNPC differentiation was also investigated on reduced graphene oxide (rGO)-containing scaffolds, that is, rGO and rGO/MoS 2 -MoO 3- x nanosheets. In darkness, hNPC differentiation into neurons increased on MoS 2 -MoO 3- x by a factor of 2.7 due to the excellent biophysical cues and further increased on rGO/MoS 2 -MoO 3- x by a factor of 4.4 due to a synergistic effect induced by the rGO. The MoO 3- x domains with antioxidant activity and LSPR absorption induced p-type doping in MoS 2 -MoO 3- x . Under photostimulation, the hNPCs on the MoS 2 -MoO 3- x exhibited higher differentiation into glial cells by a factor of 1.4, and the decrease in photo-electron current to hNPCs due to the induction of more p-type doping in the MoS 2 -MoO 3- x . While the increase in neuronal differentiation of hNPCs on rGO/MoS 2 -MoO 3- x by a factor of 1.8 was ascribed to the presence of rGO as an ultrafast electron transferor which quickly transferred photogenerated electrons to hNPCs before their transfer to free radicals, these results demonstrated the promising potential of MoS 2 -based scaffolds for applying in the controllable repair and/or regeneration of diseases/disorders related to the nervous system.

We prove the existence of relatively large Goos-Hänchen (GH) shifts for graphene in the presence of an applied strain in different crystallographic directions for p and s polarized beams. It is shown that GH shifts are smoothly increased by stretching the graphene's lattice. Moreover, we investigate the GH effect for strained graphene as a function of Fermi energy, which can be controlled by external factors such as gate voltage. We show that applied strain along zigzag and armchair orientations gives different results for GH shifts, which could provide a proper tool for the detection of strain in graphene.

Organ-on-a-chip (OOC) systems are engineered nanobiosystems to mimic the physiochemical environment of a specific organ in the body. Among various components of OOC systems, biomimetic membranes have been regarded as one of the most important key components to develop controllable biomimetic bioanalysis systems. Here, we review the preparation and characterization of biomimetic membranes in comparison with the features of the extracellular matrix. After that, we review and discuss the latest applications of engineered biomimetic membranes to fabricate various organs on a chip, such as liver, kidney, intestine, lung, skin, heart, vasculature and blood vessels, brain, and multiorgans with perspectives for further biomedical applications.

Overexpression of proteins/antigens and other gene-related sequences in the bodies could lead to significant mutations and refractory diseases. Detection and identification of assorted trace concentrations of such proteins/antigens and/or gene-related sequences remain challenging, affecting different pathogens and making viruses stronger. Correspondingly, coronavirus (SARS-CoV-2) mutations/alterations and spread could lead to overexpression of ssDNA and the related antigens in the population and brisk activity in gene-editing technologies in the treatment/detection may lead to the presence of pCRISPR in the blood. Therefore, the detection and evaluation of their trace concentrations are of critical importance. CaZnO-based nanoghosts (NGs) were synthesized with the assistance of a high-gravity technique at a 1,800 MHz field, capitalizing on the use of Rosmarinus officinalis leaf extract as the templating agent. A complete chemical, physical and biological investigation revealed that the synthesized NGs presented similar morphological features to the mesenchymal stem cells (MSCs), resulting in excellent biocompatibility, interaction with ssDNA- and/or pCRISPR-surface, through various chemical and physical mechanisms. This comprise the unprecedented synthesis of a fully inorganic nanostructure with behavior that is similar to MSCs. Furthermore, the endowed exceptional ability of inorganic NGs for detective sensing/folding of ssDNA and pCRISPR and recombinant SARS-CoV-2 spike antigen (RSCSA), along with in-situ hydrogen peroxide detection on the HEK-293 and HeLa cell lines, was discerned. On average, they displayed a high drug loading capacity of 55%, and the acceptable internalizations inside the HT-29 cell lines affirmed the anticipated MSCs-like behavior of these inorganic-NGs., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Application of materials capable of energy harvesting to increase the efficiency and environmental adaptability is sometimes reflected in the ability of discovery of some traces in an environment-either experimentally or computationally-to enlarge practical application window. The emergence of computational methods, particularly computer-aided drug discovery (CADD), provides ample opportunities for the rapid discovery and development of unprecedented drugs. The expensive and time-consuming process of traditional drug discovery is no longer feasible, for nowadays the identification of potential drug candidates is much easier for therapeutic targets through elaborate in silico approaches, allowing the prediction of the toxicity of drugs, such as drug repositioning (DR) and chemical genomics (chemogenomics). Coronaviruses (CoVs) are cross-species viruses that are able to spread expeditiously from the into new host species, which in turn cause epidemic diseases. In this sense, this review furnishes an outline of computational strategies and their applications in drug discovery. A special focus is placed on chemogenomics and DR as unique and emerging system-based disciplines on CoV drug and target discovery to model protein networks against a library of compounds. Furthermore, to demonstrate the special advantages of CADD methods in rapidly finding a drug for this deadly virus, numerous examples of the recent achievements grounded on molecular docking, chemogenomics, and DR are reported, analyzed, and interpreted in detail. It is believed that the outcome of this review assists developers of energy harvesting materials and systems for detection of future unexpected kinds of CoVs or other variants., (© 2022 The Authors. Chemical Biology & Drug Design published by John Wiley & Sons Ltd.)

Chitosan is a natural polymer with acceptable biocompatibility, biodegradability, and mechanical stability; hence, it has been widely appraised for drug and gene delivery applications. However, there has been no comprehensive assessment to tailor-make chitosan cross-linkers of various types and functionalities as well as complex chitosan-based semi- and full-interpenetrating networks for drug delivery systems (DDSs). Herein, various fabrication methods developed for chitosan hydrogels are deliberated, including chitosan crosslinking with and without diverse cross-linkers. Tripolyphosphate, genipin and multi-functional aldehydes, carboxylic acids, and epoxides are common cross-linkers used in developing biomedical chitosan for DDSs. Methods deployed for modifying the properties and performance of chitosan hydrogels, via their composite production (semi- and full-interpenetrating networks), are also cogitated here. In addition, recent advances in the fabrication of advanced chitosan hydrogels for drug delivery applications such as oral drug delivery, transdermal drug delivery, and cancer therapy are discussed. Lastly, thoughts on what is needed for the chitosan field to continue to grow is also debated in this comprehensive review article., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tissue engineering and regenerative medicine have solved numerous problems related to the repair and regeneration of damaged organs and tissues arising from aging, illnesses, and injuries. Nanotechnology has further aided tissue regeneration science and has provided outstanding opportunities to help disease diagnosis as well as treat damaged tissues. Based on the most recent findings, magnetic nanostructures (MNSs), in particular, have emerged as promising materials for detecting, directing, and supporting tissue regeneration. There have been many reports concerning the role of these nano-building blocks in the regeneration of both soft and hard tissues, but the subject has not been extensively reviewed. Here, we review, classify, and discuss various synthesis strategies for novel MNSs used in medicine. Advanced applications of magnetic nanocomposites (MG-NCs), specifically magnetic nanostructures, are further systematically reviewed. In addition, the scientific and technical aspects of MG-NC used in medicine are discussed considering the requirements for the field. In summary, this review highlights the numerous opportunities and challenges associated with the use of MG-NCs as smart nanocomposites (NCs) in tissue engineering and regenerative medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, two novel biomimetic modular peptide motifs based on the alpha - 2 subunit of type IV collagen (CO4A2) were designed and immobilized on a graphene platform to imitate integrin and heparan sulfate- (HS-) binding proteins. The in silico study was used to design 9-mer K[KGDRGD]AG and 10-mer KK[SGDRGD]AG for testing designed Integrin-Binding Peptide (dIBP) and HS-Binding Peptide (dHBP). The virtual docking technique was used to optimize the peptide motifs and their relevant receptors. Molecular dynamic (MD) simulation was used to evaluate the stability of peptide-receptor complexes. The effect of the platform on the differentiation of human mesenchymal stem cells (hMSCs) to hepatic-like cells (HLCs) was evaluated. After differentiation, some hepatic cells' molecular markers such as albumin, AFP, CK-18, and CK-19 were successfully followed. Graphene-heparan sulfate binding peptide (G-HSBP) enhances the mature hepatic markers' expression instead of control ( p ≤ 0.05). The pathological study showed that the designed platform is safe, and no adverse effects were seen till 21 days after implantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Adibi-Motlagh, Hashemi, Akhavan, Khezri, Rezaei, Zamani Amir Zakria, Siadat, Sahebghadam Lotfi and Farmany.)

A proper self-regenerating capability is lacking in human cardiac tissue which along with the alarming rate of deaths associated with cardiovascular disorders makes tissue engineering critical. Novel approaches are now being investigated in order to speedily overcome the challenges in this path. Tissue engineering has been revolutionized by the advent of nanomaterials, and later by the application of carbon-based nanomaterials because of their exceptional variable functionality, conductivity, and mechanical properties. Electrically conductive biomaterials used as cell bearers provide the tissue with an appropriate microenvironment for the specific seeded cells as substrates for the sake of protecting cells in biological media against attacking mechanisms. Nevertheless, their advantages and shortcoming in view of cellular behavior, toxicity, and targeted delivery depend on the tissue in which they are implanted or being used as a scaffold. This review seeks to address, summarize, classify, conceptualize, and discuss the use of carbon-based nanoparticles in cardiac tissue engineering emphasizing their conductivity. We considered electrical conductivity as a key affecting the regeneration of cells. Correspondingly, we reviewed conductive polymers used in tissue engineering and specifically in cardiac repair as key biomaterials with high efficiency. We comprehensively classified and discussed the advantages of using conductive biomaterials in cardiac tissue engineering. An overall review of the open literature on electroactive substrates including carbon-based biomaterials over the last decade was provided, tabulated, and thoroughly discussed. The most commonly used conductive substrates comprising graphene, graphene oxide, carbon nanotubes, and carbon nanofibers in cardiac repair were studied., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Bioengineering & Translational Medicine published by Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.)

Several pieces of research have been done on transition metal nanoparticles and their nanocomplexes as research on their physical and chemical properties and their relationship to biological features are of great importance. Among all their biological properties, the antibacterial and antimicrobial are especially important due to their high use for human needs. In this article, we will discuss the different synthesis and modification methods of silver (Ag) and gold (Au) nanoparticles and their physicochemical properties. We will also review some state-of-art studies and find the best relationship between the nanoparticles' physicochemical properties and potential antimicrobial activity. The possible antimicrobial mechanism of these types of nanoparticles will be discussed in-depth as well.

Herbal medicine wastes (HMWs) are byproducts of medicine factories, which are mainly landfilled for their environmental problems. Only bearing in mind the contamination and concerns caused by the COVID-19 pandemic and environmental emissions, the worth of herbal medicine wastes management and conversion to green products can be understood. In this work, subcritical water treatment was carried out batch-wise in a stainless tube reactor in the pressure range of 0.792-30.0 MPa, varying the temperature (127-327 °C) and time (1-60 min) of extraction. This resulted in new and green material sources, including organic acids, amino acids, and sugars. Amazingly, at very low extraction times (below 5 min) and high temperatures (above 277 °C), about 99% of HMWs were efficaciously converted to clean products by subcritical hydrothermal treatment. The results of hydrothermal extraction after 5 min indicated that at low temperatures (127-227 °C), the total organic carbon in the aqueous phase increased as the residual solid phase decreased, reaching a peak around 220 °C. Acetone soluble extracts or fat phase appeared above 227 °C and reached a maximum yield of 21% at 357 °C. Aspartic acid, threonine, and glycine were the primary amino acids; glycolic acid, formic acid, lactic acid, and acetic acid were obtained as the main organic acids, glucose, fructose, and cellobiose were substantial sugars produced from the aqueous phase after 5 min of hydrothermal subcritical hydrolysis extraction., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Green biomaterials play a crucial role in the diagnosis and treatment of diseases as well as health-related problem-solving. Typically, biocompatibility, biodegradability, and mechanical strength are requirements centered on biomaterial engineering. However, in-hospital therapeutics require an elaborated synthesis of hybrid and complex nanomaterials capable of mimicking cellular behavior. Accumulation of hazardous cations like K + in the inner and middle ear may permanently damage the ear system. We synthesized nanoplatforms based on Allium noeanum to take the first steps in developing biological porous nanomembranes for hazardous cation detection in biological media. The 1,1,1-tris[[(2'-benzyl-amino-formyl)phenoxy]methyl]ethane (A), 4-amino-benzo-hydrazide (B), and 4-(2-(4-(3-carboxy-propan-amido)benzoyl)hydrazineyl)-4-oxobutanoic acid (B1) were synthesized to obtain green ligands based on 4-X-N-(…(Y(hydrazine-1-carbonyl)phenyl)benzamide, with X denoting fluoro (B2), methoxy (B3), nitro (B4), and phenyl-sulfonyl (B5) substitutes. The chemical structure of ligand-decorated adenosine triphosphate (ATP) molecules (S-ATP) was characterized by FTIR, XRD, AFM, FESEM, and TEM techniques. The cytotoxicity of the porous membrane was patterned by applying different cell lines, including HEK-293, PC12, MCF-7, HeLa, HepG2, and HT-29, to disclose their biological behavior. The morphology of cultured cells was monitored by confocal laser scanning microscopy. The sensitivity of S-ATP to different cations of Na + , Mg 2+ , K + , Ba 2+ , Zn 2+ , and Cd 2+ was evaluated by inductively coupled plasma atomic emission spectroscopy (ICP-AES) in terms of extraction efficiency (η). For pH of 5.5, the η of A-based S-ATP followed the order Na + (63.3%) > Mg 2+ (62.1%) > Ba 2+ (7.6%) > Ca 2+ (5.5%); while for pH of 7.4, Na + (37.0%) > Ca 2+ (33.1%) > K + (25 . 7%). The heat map of MTT and dose-dependent evaluations unveiled acceptable cell viability of more than 90%. The proposed green porous nanomembranes would pave the way to use multifunctional green porous nanomembranes in biological membranes., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Viral diseases have long been among the biggest challenges for healthcare systems around the world. The recent Coronavirus Disease 2019 (COVID-19) pandemic is an example of how complicated the situation can get if we are not prepared to combat a viral outbreak in time, which brings up the need for quick and affordable biosensing platforms and vast knowledge of potential antiviral effects and drug/gene delivery opportunities. The same challenges have also existed for nonviral immunogenic disorders. Nanomedicine is considered a novel candidate for effectively overcoming these worldwide challenges. Among the versatile nanomaterials commonly used in biomedical applications, graphene has recently earned much attention thanks to its special and inspiring physicochemical properties, such as its large surface area, efficient thermal/electrical properties, carbon-based chemical purity with controllable biocompatibility, easy functionalization, capability of single-molecule detection, anticancer characteristics, 3D template feature in tissue engineering, and, in particular, antibacterial/antiviral activities. In this Review, the most important and challenging viruses of our era, such as human immunodeficiency virus, Ebola, SARS-CoV-2, norovirus, and hepatitis virus, and immunogenic disorders, such as asthma, Alzheimer's disease, and Parkinson's disease, in which graphene-based nanomaterials can effectively take part in the prevention, detection, treatment, medication, and health effect issues, have been covered and discussed.

The design of advanced nanobiomaterials to improve analytical accuracy and therapeutic efficacy has become an important prerequisite for the development of innovative nanomedicines. Recently, phospholipid nanobiomaterials including 2-methacryloyloxyethyl phosphorylcholine (MPC) have attracted great attention with remarkable characteristics such as resistance to nonspecific protein adsorption and cell adhesion for various biomedical applications. Despite many recent reports, there is a lack of comprehensive review on the phospholipid nanobiomaterials from synthesis to diagnostic and therapeutic applications. Here, we review the synthesis and characterization of phospholipid nanobiomaterials focusing on MPC polymers and highlight their attractive potentials for applications in micro/nanofabricated fluidic devices, biosensors, lab-on-a-chip, drug delivery systems (DDSs), COVID-19 potential usages for early diagnosis and even treatment, and artificial extracellular matrix scaffolds for cellular engineering.

The coronavirus disease (COVID-19) pandemic, which has spread around the world, caused the death of many affected patients, partly because of the lack of oxygen arising from impaired respiration or blood circulation. Thus, maintaining an appropriate level of oxygen in the patients' blood by devising alternatives to ventilator systems is a top priority goal for clinicians. The present review highlights the ever-increasing application of nanobubbles (NBs), miniature gaseous vesicles, for the oxygenation of hypoxic patients. Oxygen-containing NBs can exert a range of beneficial physiologic and pharmacologic effects that include tissue oxygenation, as well as tissue repair mechanisms, antiinflammatory properties, and antibacterial activity. In this review, we provide a comprehensive survey of the application of oxygen-containing NBs, with a primary focus on the development of intravenous platforms. The multimodal functions of oxygen-carrying NBs, including antimicrobial, antiinflammatory, drug carrying, and the promotion of wound healing are discussed, including the benefits and challenges of using NBs as a treatment for patients with acute hypoxemic respiratory failure, particularly due to COVID-19., Competing Interests: The authors declare no competing financial interest., (© 2021 American Chemical Society.)

Efficient strategies to promote microvascularization in vascular tissue engineering, a central priority in regenerative medicine, are still scarce; nano- and micro-sized aggregates and spheres or beads harboring primitive microvascular beds are promising methods in vascular tissue engineering. Capillaries are the smallest type and in numerous blood vessels, which are distributed densely in cardiovascular system. To mimic this microvascular network, specific cell components and proangiogenic factors are required. Herein, advanced biofabrication methods in microvascular engineering, including extrusion-based and droplet-based bioprinting, Kenzan, and biogripper approaches, are deliberated with emphasis on the newest works in prevascular nano- and micro-sized aggregates and microspheres/microbeads., (© 2021. The Author(s).)

Background: Unique properties of graphene and its derivatives make them attractive in the field of nanomedicine. However, the mass application of graphene might lead to side effects, which has not been properly addressed in previous studies, especially with regard to its effect on the cell cycle., Methods: The effect of two concentrations (100 and 200 μg/mL) of nano- and microsized graphene oxide (nGO and mGO) on apoptosis, cell cycle, and ROS generation was studied. The effect of both sizes on viability and genotoxicity of the embryonic fibroblast cell cycle was evaluated. MTT and flow cytometry were applied to evaluate the effects of graphene oxide (GO) nanosheets on viability of cells. Apoptosis and cell cycle were analyzed by flow cytometry., Results: The results of this study showed that GO disturbed the cell cycle and nGO impaired cell viability by inducing cell apoptosis. Interestingly, both nGO and mGO blocked the cell cycle in the S phase, which is a critical phase of the cell cycle. Upregulation of TP53 -gene transcripts was also detected in both nGO- and mGO-treated cells compared to the control, especially at 200 μg/mL. DNA content of the treated cells increased; however, because of DNA degradation, its quality was decreased., Conclusion: In conclusion, graphene oxide at both nano- and micro-scale damages cell physiology and increases cell population in the S phase of the cell cycle., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Hashemi et al.)

An oxygen nanoshuttle based on a reduced graphene oxide/copper peroxide (rGO/CuO 2 ) nanocomposite has been presented to deliver in situ oxygen nanobubbles (O 2 NBs) for combating bacterial infections. In the presence of rGO, the solid source of oxygen (i.e., CuO 2 ) was decomposed (in response to environmental conditions such as pH and temperature) into O 2 NBs in a more controllable and long-lasting trend (from 60 to 144 h). In a neutral buffer, the O 2 NBs experienced growth and collapse evolutions, creating a dynamic micro-nanoenvironment around the nanocomposite. In addition to effective battling against methicillin-resistant Staphylococcus aureus bacteria, the O 2 NBs demonstrated superior antibacterial properties on Gram-positive S. aureus to those on Gram-negative Escherichia coli bacteria, especially in the presence of rGO. In fact, the rGO contents could provide synergistic effects through harvesting some respiratory electrons (leading to striking interruption of the bacterial respiratory pathway) in one side and transferring them into the O 2 NBs, resulting in nanoscale reactive oxygen species (ROS) generation in another side. Moreover, near-infrared laser irradiation induced more damage to the cell membrane due to the synergistic effects of local heat elevation and catalyzing the release/collapse of NBs imposing mechanical disruptions. Our results show that the O 2 -containing nanoshuttles can effectively be used as intelligent and controllable anti-infection nanorobots in upcoming graphene-based nanobiomedical applications.

Triboelectric nanogenerators (TENGs) offer an emerging market of self-sufficient power sources, converting the mechanical energy of the environment to electricity. Recently reported high power densities for the TENGs provide new applications opportunities, such as self-powered sensors. Here in this research, a flexible graphene oxide (GO) paper was fabricated through a straightforward method and utilized as the electrode of TENGs. Outstanding power density as high as 1.3 W.m -2 , an open-circuit voltage up to 870 V, and a current density of 1.4 µA.cm -2 has been extracted in vertical contact-separation mode. The all-flexible TENG has been employed as a self-powered humidity sensor to investigate the effect of raising humidity on the output voltage and current by applying mechanical agitation in two forms of using a tapping device and finger tapping. Due to the presence of superficial functional groups on the GO paper, water molecules are inclined to be adsorbed, resulting in a considerable reduction in both generated voltage (from 144 V to 14 V) and current (from 23 µA to 3.7 µA) within the range of relative humidity of 20% to 99%. These results provide a promising applicability of the first suggested sensitive self-powered GO TENG humidity sensor in portable/wearable electronics.

Free polymer graphene aerogel nanoparticles (GA NPs) were synthesized by using reduction/aggregation of graphene oxide (GO) sheets in the presence of vitamin C (as a biocompatible reductant agent) at a low temperature (40 °C), followed by an effective sonication. Synthesis of GA NPs in doxorubicin hydrochloride (DOX)-containing solution results in the simultaneous synthesis and drug loading with higher performance (than that of the separately synthesized and loaded samples). To investigate the mechanism of loading and the capability of GA NPs in the loading of other drug structures, two groups of ionized (DOX, Amikacin sulfate and, d-glucosamine hydrochloride) and non-ionized (Paclitaxel (PTX)) drugs were examined. Furthermore, the relationship between the bipolar level of DOX solution (contributing to H-bonding of DOX and GO) and the amount of DOX loading was investigated. The DOX showed higher loading (>3 times) than PTX, as anticancer drugs. Since both DOX and PTX possess aromatic structures, the higher loading of DOX was assigned to its positive partial charge and ionized nature. Accordingly, other drugs (having positive partial charge and ionized nature, but no aromatic structure) such as Amikacin sulfate and d-glucosamine hydrochloride presented higher loading than PTX. These results indicated that although the π-π interactions induced by aromatic structures are important in drug loading, the electrostatic interaction of ionized drugs with GO (especially through H-bonding) is the dominant mechanism. DOX-loaded GANPs showed high pH-sensitive release (equivalent to the carrier weight) after 5 days, which can indicate benefits in tumor cell acidic microenvironments in-vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The reverse osmosis (RO) desalination capability of hydrogenated and hydroxylated graphene nanomesh membranes (GNMs) inspired by the morphology of carbon nitride (C 2 N) has been studied by using molecular dynamics simulation. As an advantage, water permeance of the GNMs is found to be several orders of magnitude higher than that of the available RO filters and comparable with highly strained C 2 N (S-C 2 N) as follows: 6,6-H,OH > 12-H > S-C 2 N > 5,5-H,OH > 10-H. The reverse order is found for salt rejection, regardless of S-C 2 N. The hydrophilic character of the incorporated -OH functional group is believed to be responsible for linking the water molecules in feed and permeate sides via the formation of strong hydrogen bonds. This leads to a remarkable reduction in resistance of water molecules during penetration across GNMs. In fact, water permeance and salt rejection of the GNMs are controllable by adjusting the effective size and chemistry of their nanopores, while these kinds of adjustments are principally impossible for C 2 N, resulting in limiting the water permeance. More importantly, the C 2 N nanofilter works efficiently only under high tensile strain, which is not so straightforward in practice. These observations are also verified by computing electrostatic potential map interaction and barrier energies for transportation of water molecules/ions through GNMs based on quantum chemistry aspects.

Ischemic cerebral stroke is a major cause of death and morbidity. Currently, no neuroprotective agents have been shown to impact the clinical outcomes in cerebral stroke cases. Here, we report therapeutic effects of Se nanoparticles on ischemic stroke in a murine model. Anti-transferrin receptor monoclonal antibody (OX26)-PEGylated Se nanoparticles (OX26-PEG-Se NPs) were designed and synthesized and their neuroprotective effects were measured using in vitro and in vivo approaches. We demonstrate that administration of the biodegradable nanoparticles leads to resolution of brain edema, protection of axons in hippocampus region, and myelination of hippocampal area after cerebral ischemic stroke. Our nanoparticle design ensures efficient targeting and minimal side effects. Hematological and biochemical analyses revealed no undesired NP-induced changes. To gain mechanistic insights into the therapeutic effects of these particles, we characterized the changes to the relevant inflammatory and metabolic signaling pathways. We assessed metabolic regulator mTOR and related signaling pathways such as hippo, Ubiquitin-proteasome system (ERK5), Tsc1/Tsc2 complex, FoxO1, wnt/β-catenine signaling pathway. Moreover, we examined the activity of jak2/stat3 signaling pathways and Adamts1, which are critically involved in inflammation. Together, our study provides a promising treatment strategy for cerebral stroke based on Se NP induced suppression of excessive inflammation and oxidative metabolism.

Presently, clinical nanomedicine and nanobiotechnology have impressively demanded the generation of new organic/inorganic analogues of graphene (as one of the intriguing biomedical research targets) for stem-cell-based tissue engineering. Among different shapes of graphene, three-dimensional (3D) graphene foams (GFs) are highly promising candidates to provide conditions for mimicking in vivo environments, affording effective cell attachment, proliferation,and differentiation due to their unique properties. These include the highest biocompatibility among nanostructures, high surface-to-volume ratio, 3D porous structure (to provide a homogeneous/isotropic growth of tissues), highly favorable mechanical characteristics, and rapid mass and electron transport kinetics (which are required for chemical/physical stimulation of differentiated cells). This review aims to describe recent and rapid advances in the fabrication of 3D GFs, together with their use in tissue engineering and regenerative nanomedicine applications. Moreover, we have summarized a broad range of recent studies about the behaviors, biocompatibility/toxicity,and biodegradability of these materials, both in vitro and in vivo. Finally, the highlights and challenges of these 3D porous structures, compared to the current polymeric scaffold competitors, are discussed.

Interaction of nanoplatforms with biomolecules in biological fluids alters nanoplatforms approach to target tissue and deliver their cargo. Here in, three nanoplatforms were utilized as a carrier to detect the effects of subsequent biomolecules on gene delivery using NIR thermal therapy. Nanoplatforms included; graphene oxide coated gold nanorods (NR@GO), PEGylated NR@GO (NR@GO-PEG) and poly L arginine functionalized NR@GO-PEG (NR@GO-PEG-PLArg). Results indicated that incubation of nanoplatforms in different concentrations of human plasma induced the evolution of layer of proteins (corona) with different thickness on the surface of nanoplatforms. Protein corona decreased the surface charge and optical properties of nanoplatforms. Corona subunits of ITIH, HAS and APOs protein family were extracted from NR@GO-PEG-PLArg surface that play a major role in cellular internalization of nanoplatforms. Moreover, NR@GO-PEG-PLArg remarkably targeted the cancer cells due to uncovered long linear chains of targeting agent (PLArg). The process of gene release and activating apoptotic pathway were enhanced by NIR thermal therapy, which could disrupt the electrostatic interactions and release the protein corona and genes from the surface of nanoplatforms. In conclusion, modification of nanoplatforms with targeting agents could alter the composition of corona toward well interaction with cell and deliver the therapeutic agent., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: MicroRNA-101 (miR-101) is an intense cancer suppressor with special algorithm to target a wide range of pathways and genes which indicates the ability to regulate apoptosis, cellular stress, metastasis, autophagy, and tumor growth. Silencing of some genes such as Stathmin1 with miR-101 can be interpreted as apoptotic accelerator and autophagy suppressor. It is hypothesized that hybrid microRNA (miRNA) delivery structures based on cationized graphene oxide (GO) could take superiority of targeting and photothermal therapy to suppress the cancer cells., Materials and Methods: In this study, GO nanoplatforms were covalently decorated with polyethylene glycol (PEG) and poly-l-arginine (P-l-Arg) that reduced the surface of GO and increased the near infrared absorption ~7.5-fold higher than nonreduced GO., Results: The prepared nanoplatform [GO-PEG-(P-l-Arg)] showed higher miRNA payload and greater internalization and facilitated endosomal scape into the cytoplasm in comparison with GO-PEG. Furthermore, applying P-l-Arg, as a targeting agent, greatly improved the selective transfection of nanoplatform in cancer cells (MCF7, MDA-MB-231) in comparison with immortalized breast cells and fibroblast primary cells. Treating cancer cells with GO-PEG-(P-l-Arg)/miR-101 and incorporating near infrared laser irradiation induced 68% apoptosis and suppressed Stathmin1 protein., Conclusion: The obtained results indicated that GO-PEG-(P-l-Arg) would be a suitable targeted delivery system of miR-101 transfection that could downregulate autophagy and conduct thermal stress to activate apoptotic cascades when combined with photothermal therapy., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Recent insights into the nanomedicine have revealed that nanoplatforms enhance the efficacy of carrier in therapeutic applications. Here, multifunctional nanoplatforms were utilized in miRNA-101 delivery and NIR thermal therapy to induce apoptosis in breast cancer cells. Au nanorods (NRs) or nanospheres (NSs) covered with graphene oxide (GO) were prepared and functionalized with polyethylene glycol as a stabilizer and poly-L-arginine (P-L-Arg) as a targeting agent. In nanoplatforms, coupling Au@GO prepared stable structures with higher NIR reactivity. P-L-Arg substantially enhanced the cellular uptake and gene retardation of stuffs coated by them. However, rod-shape nanoplatforms indicated better performance in cellular uptake and gene transfection than spherical ones. NIR thermal therapy was implemented to improve gene release and in synergy with miRNA-101 activated the apoptotic pathway and decreased the viability of breast cancer cell (<20%). Briefly, presented delivery systems are potentially efficient in distinguishing cancer cells, miRNA internalization and controlling apoptosis of cancer cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Organ ischemia with inadequate oxygen supply followed by reperfusion (which initiates a complex of inflammatory responses and oxidative stress) occurs in different clinical conditions and surgical procedures including stroke, myocardial infarction, limb ischemia, renal failure, organ transplantation, free-tissue-transfer, cardiopulmonary bypass, and vascular surgery. Even though pharmacological treatments protect against experimental ischemia reperfusion (I/R) injury, there has not been enough success in their application for patient benefits. The main hurdles in the treatment of I/R injury are the lack of diagnosis tools for understanding the complicated chains of I/R-induced signaling events, especially in the acute phase after ischemia, determining the affected regions of the tissue over time, and then, targeting and safe delivery of antioxidants, drugs, peptides, genes and cells to the areas requiring treatment. Besides the innate antioxidant and free radical scavenging properties, some nanoparticles also show higher flexibility in drug delivery and imaging. This review highlights three main approaches in nanoparticle-mediated targeting of I/R injury: nanoparticles (1) as antioxidants for reducing tissue oxidative stress, (2) for targeted delivery of therapeutic agents to the ischemic regions or cells, and (3) for imaging I/R injury at the molecular, cellular or tissue level and monitoring its evolution using contrasts induced by nanoparticles. These approaches can also be combined to realize so called theranostics for providing simultaneous diagnosis of ischemic regions and treatments by targeted delivery.

Recent studies showed that a large amount of graphene oxide accumulated in kidney and liver when it injected intravenously. Evaluation of lethal and apoptosis gene expression in these tissues, which are under stress is very important. In this paper the in vivo dose-dependent effects of graphene oxide and reduced graphene oxide nanoplatelets on kidney and liver of mice were studied. Balb/C mice were treated by 20mg/kg body weight of nanoplatelets. Molecular biology analysis showed that graphene nanoplatelets injected intravenously lead to overexpression of BAX gene in both kidney and liver tissues (P≥0.01). In addition these nanoparticles significantly increase BCL2 gene expression in both kidney and liver tissues (P≥0.05). Graphene significantly increase level of SGPT in groups 1 (220.64±13), 2 (164.44±9.3) in comparison to control group (P≤0.05). Also in comparison with control group (148.11±10.4), (P≤0.05), the level of SGOT in groups 1(182.01±12.6) and 2 (178.2±2.2) significantly increased., (Copyright © 2016. Published by Elsevier B.V.)

In recent years, quantum dots (QDs) have been widely used in upcoming nanotechnology-based solar cells, light-emitting diodes and even bioimaging, due to their tunable optical properties and excellent quantum yields. But, such nanostructures are currently constituted by heavy elements which can threat the human health and living environment. Hence, in this work, the in vivo effects of CdTe nanocrystals (NCs) (as one of the promising QDs) on spermatozoa of male mice and subsequently on fertility of female mice were investigated, for the first time. To do this, CdTe NCs were synthesized through an environment-friendly (aqueous-based solution) method. The sperm cells presented a high potential for uptake of the heavy QDs. Meantime, the NCs exhibited concentration-dependent adverse effects on morphology, viability, kinetic characteristics and DNA of the spermatozoa. At low concentration of 0.1μg/mL, the NCs showed a moderate toxicity (~25% reduction in viability and motility of the spermatozoa), while remarkable toxicities were observed at higher concentrations of 1.0-100μg/mL (~67% reduction in viability and motility for 100μg/mL). Furthermore, significant in vitro DNA fragmentation of the spermatozoa was observed at CdTe concentrations ≥10μg/mL. In vivo toxicity of the NCs was found lower than the in vitro toxicity. Nevertheless, the in vivo destructive effects of the NCs still caused ~34% reduction in viability as well as motility and ~5% damages in DNA of male mice spermatozoa. These resulted in ~26% decrease in fertility and gestation of female mice, along with an overall hormone secretion during the pregnancy, and ~39% reduction in viability of pups/pregnant females., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The present study analyzed the dose-dependent cyto- and genotoxicity of graphene oxide and reduced graphene oxide on spermatogonial stem cells (SSCs) for the first time. The results showed that graphene oxide significantly increased oxidative stress at concentrations of 100 and 400μg/ml, while low concentrations did not have a significant effect. In addition, according to the MTT assay, the cell number decreased in high-concentration (100 and 400μg/ml) graphene oxide-treated samples compared to untreated cells. However, a reduced graphene-treated sample demonstrated a significant increase in cell number. Moreover, microscopic analysis found high concentrations of graphene nanosheets in cell culture medium that reduced the number of colonies and colony forming cells. We conclude that a high concentration of graphene can be toxic to SSCs. However, such toxicity can be reduced by the surface modification of graphene nanomaterials., (Copyright © 2016 Elsevier B.V. All rights reserved.)

A remote controllable working graphite nanostructured swimmer based on a graphene jet nanomotor has been demonstrated for the first time. Graphite particles with pyramidal-like morphologies were fabricated by the creation of suitable defects in wide high-purity graphite flakes followed by a severe sonication. The particles were able to be self-exfoliated in water after Na intercalation between the graphene constituents. The self-exfoliation resulted in jet ejection of graphene flakes from the end of the swimmers (with speeds as high as ∼7000 m/s), producing a driving force (at least ∼0.7 L (pN) where L (μm) is swimmer size) and consequently the motion of the swimmer (with average speed of ∼17-40 μm/s). The jet ejection of the graphene flakes was assigned to the explosion of H2 nanobubbles produced between the Na intercalated flakes. The direction of motion of the swimmers equipped with TiO2 nanoparticles (NPs) can be controlled by applying a magnetic field in the presence of UV irradiation (higher UV intensity, lower radius of rotation). In fact, the negative surface charge of the graphene flakes of the swimmers increased by UV irradiation due to transferring the photoexcited electrons of TiO2 NPs into the flakes. Because of higher production of H2 nanobubbles under UV irradiation, the speed of swimmers exposed to UV light significantly increased. In contrast, UV irradiation with various intensities could not affect total distance traversed by the self-exfoliated swimmers having the same initial sizes. These confirmed the mass ejection mechanism for motion of the swimmers. The self-exfoliation of swimmers (and so their motion) occurred only in water (and not, e.g., in organic solutions). Such swimmers promise the design of remote controllable nanovehicles with the capability of initiating and/or improving their operations in response to environmental changes in order to realize broad ranges of versatile and fantastic nanotechnology-based applications.

The graphene-based materials with unique, versatile, and tunable properties have brought new opportunities for the leading edge of advanced nanobiotechnology. In this regard, the use of graphene in gene delivery applications is still at early stages. In this study, we successfully designed a new complex of carboxylated-graphene (G-COOH) with ethidium bromide (EtBr) and used it as a nanovector for efficient gene delivery into the AGS cells. G-COOH, with carboxyl functions on its surface, in the presence of EtBr, formaldehyde, and cyclohexylisocyanide were participated in Ugi four component reaction to fabricate a stable amphiphilic graphene-EtBr (AG-EtBr) composite. The coupling reaction was confirmed by further analyses with FT-IR, AFM, UV-vis, Raman, photoluminescence, EDS, and XPS. The AG-EtBr nanocomposite was able to interact with a plasmid DNA (pDNA). This nanocomposite has been applied for transfection of cultured mammalian cells successfully. Moreover, the AG-EtBr composites showed a remarkable decreased cytotoxicity in compared to EtBr. Interestingly, the advantages of AG-EtBr in cell transfection are more dramatic (3-fold higher) than Lipofectamine2000 as a commercial nonviral vector. To the best of our knowledge, this is the first report in which EtBr is used as an intercalating agent along with graphene to serve as a new vehicle for gene delivery application.

Although graphene/stem cell-based tissue engineering has recently emerged and has promisingly and progressively been utilized for developing one of the most effective regenerative nanomedicines, it suffers from low differentiation efficiency, low hybridization after transplantation and lack of appropriate scaffolds required in implantations without any degrading in functionality of the cells. In fact, recent studies have demonstrated that the unique properties of graphene can successfully resolve all of these challenges. Among various stem cells, neural stem cells (NSCs) and their neural differentiation on graphene have attracted a lot of interest, because graphene-based neuronal tissue engineering can promisingly realize the regenerative therapy of various incurable neurological diseases/disorders and the fabrication of neuronal networks. Hence, in this review, we further focused on the potential bioapplications of graphene-based nanomaterials for the proliferation and differentiation of NSCs. Then, various stimulation techniques (including electrical, pulsed laser, flash photo, near infrared (NIR), chemical and morphological stimuli) which have recently been implemented in graphene-based stem cell differentiations were reviewed. The possibility of degradation of graphene scaffolds (NIR-assisted photodegradation of three-dimensional graphene nanomesh scaffolds) was also discussed based on the latest achievements. The biocompatibility of graphene scaffolds and their probable toxicities (especially after the disintegration of graphene scaffolds and distribution of its platelets in the body), which is still an important challenge, were reviewed and discussed. Finally, the initial recent efforts for fabrication of neuronal networks on graphene materials were presented. Since there has been no in vivo application of graphene in neuronal regenerative medicine, we hope that this review can excite further and concentrated investigations on in vivo (and even in vitro) neural proliferation, stimulation and differentiation of stem cells on biocompatible graphene scaffolds having the potential of degradability for the generation of implantable neuronal networks.

Electro-reduction behavior of testosterone at reduced graphene oxide/glassy carbon electrode (rGO/GCE) was studied. Cationic surfactant cetyltrimethylammonium bromide (CTAB) enhanced the reduction peak of testosterone. In borate buffer (pH5.4) CTAB-testosterone showed a reduction peak at -1.1 V (versus, Ag/AgCl). The increment of peak current obtained by deducting the reduction peak current of the CTAB-testosterone was rectilinear with testosterone concentration in the range of 2.0 to 210.0 nM, with a detection limit of 0.1 nM. The sensor was used for quantification of testosterone in biological fluids and drug., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Curcumin (as a natural reductant material) was utilized for green reduction and functionalization of chemically exfoliated graphene oxide (GO) sheets. The π-π attachment of the curcumin molecules onto the curcumin-reduced graphene oxide (rGO) sheets was confirmed by Raman and Fourier transform infrared spectroscopies. Zeta potential of the GO sheets decreased from about -40 mV to -20 mV, after the green reduction and functionalization. The probable cytotoxicity of the curcumin-rGO sheets was studied through their interactions with two human breast cancer cell lines (MDA-MB-231 and SKBR3 cell lines) and a normal cell line (mouse fibroblast L929 cell line). The curcumin-rGO sheet with concentrations <70 μg/mL in the cell culture medium, not only exhibited no significant toxicity and/or cell morphological changes, but also caused some cell growths (~25% after 48 h incubation time). Nevertheless, at 70 μg/mL, initiation of some cell morphological changes was observed. At higher concentrations (e.g., 100 μg/mL), some slight cytotoxic effects (resulting in ~15-25% cell destruction) were detected by MTT assay. In addition, the interaction of the rGO sheets and cells resulted in apoptosis as well as morphological transformation of the cells (from elongated to roundup morphology). These results indicated the concentration-dependent toxicity of functionalized-rGO nanomaterials (here, curcumin-rGO) at the threshold concentration of ~100 μg/mL., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the 'personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.

Reduced graphene oxide nanomeshes (rGONMs), as p-type semiconductors with band-gap energy of ∼ 1 eV, were developed and applied in near infrared (NIR) laser stimulation of human neural stem cells (hNSCs) into neurons. The biocompatibility of the rGONMs in growth of hNSCs was found similar to that of the graphene oxide (GO) sheets. Proliferation of the hNSCs on the GONMs was assigned to the excess oxygen functional groups formed on edge defects of the GONMs, resulting in superhydrophilicity of the surface. Under NIR laser stimulation, the graphene layers (especially the rGONMs) exhibited significant cell differentiations, including more elongations of the cells and higher differentiation of neurons than glia. The higher hNSC differentiation on the rGONM than the reduced GO (rGO) was assigned to the stimulation effects of the low-energy photoexcited electrons injected from the rGONM semiconductors into the cells, while the high-energy photoelectrons of the rGO (as a zero band-gap semiconductor) could suppress the cell proliferation and/or even cause cell damages. Using conventional heating of the culture media up to ∼ 43 °C (the temperature typically reached under the laser irradiation), no significant differentiation was observed in dark. This further confirmed the role of photoelectrons in the hNSC differentiation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Nanoparticles of high-Z elements exhibit stronger photoelectric effects than soft tissues under gamma irradiation. Hence, they can be used as effective radiosensitizers for increasing the efficiency of current radiotherapy. In this work, superparamagnetic zinc ferrite spinel (ZnFe2O4) nanoparticles were synthesized by a hydrothermal reaction method and used as radiosensitizers in cancer therapy. The magnetic nanoparticles showed fast separation from solutions (e.g., ~1 min for 2 mg mL(-1) of the nanoparticles in ethanol) by applying an external magnetic field (~1T). The ZnFe2O4 nanoparticles were applied in an in vitro radiotherapy of lymph node carcinoma of prostate cells (as high radioresistant cells) under gamma irradiation of (60)Co source. The nanoparticles exhibited no significant effects on the cancer cells up to the high concentration of 100 μg mL(-1), in the absence of gamma irradiation. The gamma irradiation alone (2Gy dose) also showed no significant effects on the cells. However, gamma irradiation in the presence of 100 μg mL(-1) ZnFe2O4 nanoparticles resulted in ~53% inactivation of the cells (~17 times higher than the inactivation that occurred under gamma irradiation alone) after 24h. The higher cell inactivation was assigned to interaction of gamma radiation with nanoparticles (photoelectric effect), resulting in a high level electron release in the media of the radioresistant cells. Our results indicated that ZnFe2O4 nanoparticles not only can be applied in increasing the efficiency of radiotherapy, but also can be easily separated from the cell environment by using an external magnetic field after the radiotherapy., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Graphene oxide nanoplatelets (GONPs) with extremely sharp edges (lateral dimensions ∼ 20-200 nm and thicknesses <2 nm) were applied in extraction of the overexpressed guanine synthesized in the cytoplasm of leukemia cells. The blood serums containing the extracted guanine were used in differential pulse voltammetry (DPV) with reduced graphene oxide nanowall (rGONW) electrodes to develop fast and ultra-sensitive electrochemical detection of leukemia cells at leukemia fractions (LFs) of ∼ 10(-11) (as the lower detection limit). The stability of the DPV signals obtained by oxidation of the extracted guanine on the rGONWs was studied after 20 cycles. Without the guanine extraction, the DPV peaks relating to guanine oxidation of normal and abnormal cells overlapped at LFs <10(-9), and consequently, the performance of rGONWs alone was limited at this level. As a benchmark, the DPV using glassy carbon electrodes was able to detect only LFs ∼ 10(-2). The ultra-sensitivity obtained by this combination method (guanine extraction by GONPs and then guanine oxidation by rGONWs) is five orders of magnitude better than the sensitivity of the best current technologies (e.g., specific mutations by polymerase chain reaction) which not only are expensive, but also require a few days for diagnosis.

Graphene oxide (GO) sheets functionalized by aminopropylsilyl groups (8.0 wt.%) were labeled by (198,199)Au nanoparticle radioisotopes (obtained through reduction of HAuCl4 in sodium citrate solution followed by thermal neutron irradiation) for fast in vivo targeting and SPECT imaging (high purity germanium-spectrometry) of tumors. Using instant thin layer chromatography method, the physicochemical properties of the amino-functionalized GO sheets labeled by (198,199)Au NPs ((198,199)Au@AF-GO) were found to be highly stable enough in organic phases, e.g. a human serum, to be reliably used in bioapplications. In vivo biodistribution of the (198,199)Au@AF-GO composite was investigated in rats bearing fibrosarcoma tumor after various post-injection periods of time. The (198,199)Au@AF-GO nanostructure exhibited a rapid as well as high tumor uptake (with uptake ratio of tumor to muscle of 167 after 4h intravenous injection) that resulted in an efficient tumor targeting/imaging. Meantime, the low lipophilicity of the (198,199)Au@AF-GO caused to its fast excretion (~24 h) throughout the body by the kidneys (as also confirmed by the urinary tract). Because of the short half-life of (198,199)Au radioisotopes, the (198,199)Au@AF-GO with an excellent tumor targeting/imaging and fast washing out from the body can be suggested as one of the most effective and promising nanomaterials in nanotechnology-based cancer diagnosis and therapy., (Copyright © 2014 Elsevier B.V. All rights reserved.)