Cytotoxicity Profile of Highly Hydrogenated Graphene

Graphene and its graphene‐related counterparts have been considered the future of advanced nanomaterials owing to their exemplary properties. An increase in their potential applications in the biomedical field has led to serious concerns regarding their safety and impact on health. To understand the toxicity profile for a particular type of graphene utilized in a given application, it is important to recognize the differences between the graphene‐related components and correlate their cellular toxicity effects to the attributed physiochemical properties. In this study, the cytoxicity effects of highly hydrogenated graphene (HHG) and its graphene oxide (GO) counterpart on the basis of in vitro toxicological assessments are reported and the effects correlated with the physiochemical properties of the tested nanomaterials. Upon 24 h exposure to the nanomaterials, a dose‐dependent cellular cytotoxic effect was exhibited and the HHG was observed to be more cytotoxic than its GO control. Detailed characterization revealed an extensive C?H sp³ network on the carbon backbone of HHG with few oxygen‐containing groups, as opposed to the presence of large amounts of oxygen‐containing groups on the GO. It is therefore hypothesized that the preferential adsorption of micronutrients on the surface of the HHG nanomaterial by means of hydrophobic interactions resulted in a reduction in the bioavailability of nutrients required for cellular viability. The nanotoxicological profile of highly hydrogenated graphene is assessed for the first time in our study, thereby paving the way for further evaluation of the toxicity risks involved with the utilization of various graphene‐related nanomaterials in the real world.     

Mechanisms and measurements of nanomaterial-induced oxidative damage to DNA

Many of the current investigations on the environmental and human health risks of engineered nanomaterials focus on their short-term acute toxicity. However, the long-term chronic effects of nanomaterials on living systems, and in particular, on the genetic components of living systems, also warrant attention. An increasing number of nanomaterial safety studies include an assessment of genotoxicity as part of the overall risk evaluation. The potential of nanomaterials to directly or indirectly promote the formation of reactive oxygen species is one of the primary steps in their genotoxic repertoire. The subsequent modification of genomic DNA by reactive oxygen species could lead to the development of mutagenesis, carcinogenesis, or other age-related diseases if the DNA damage is not repaired. This review focuses on the interactions of nanomaterials with DNA and specifically on the capacity of some nanomaterials to induce oxidative damage to DNA. A critical assessment of the analytical methodology and the potential biochemical mechanisms involved in nanomaterial induction of oxidative damage to DNA is presented, results obtained for the various studies with each nanomaterial are compared, and recommendations for future research are discussed. Researchers should consider, among other experimental recommendations, (1) the application of more chromatography-based and mass-spectrometry-based analytical techniques to the assessment of oxidative damage to DNA to facilitate an enhanced understanding of DNA damage mechanisms and (2) the verification of cellular viability before conducting genotoxicity assays to reduce the impact of fragmented DNA, formed as a consequence of cell death, on DNA damage measurements.     

Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake

Delivery and toxicity are critical issues facing nanomedicine research. Currently, there is limited understanding and connection between the physicochemical properties of a nanomaterial and its interactions with a physiological system. As a result, it remains unclear how to optimally synthesize and chemically modify nanomaterials for in vivo applications. It has been suggested that the physicochemical properties of a nanomaterial after synthesis, known as its "synthetic identity", are not what a cell encounters in vivo. Adsorption of blood components and interactions with phagocytes can modify the size, aggregation state, and interfacial composition of a nanomaterial, giving it a distinct "biological identity". Here, we investigate the role of size and surface chemistry in mediating serum protein adsorption to gold nanoparticles and their subsequent uptake by macrophages. Using label-free liquid chromatography tandem mass spectrometry, we find that over 70 different serum proteins are heterogeneously adsorbed to the surface of gold nanoparticles. The relative density of each of these adsorbed proteins depends on nanoparticle size and poly(ethylene glycol) grafting density. Variations in serum protein adsorption correlate with differences in the mechanism and efficiency of nanoparticle uptake by a macrophage cell line. Macrophages contribute to the poor efficiency of nanomaterial delivery into diseased tissues, redistribution of nanomaterials within the body, and potential toxicity. This study establishes principles for the rational design of clinically useful nanomaterials.     

Toxicity assessment of nanomaterials: methods and challenges

The increasing use of nanomaterials in consumer and industrial products has aroused global concern regarding their fate in biological systems, resulting in a demand for parallel risk assessment. A number of studies on the effects of nanoparticles in in vitro and in vivo systems have been published. However, there is still a need for further studies that conclusively establish their safety/toxicity, due to the many experimental challenges and issues encountered when assessing the toxicity of nanomaterials. Most of the methods used for toxicity assessment were designed and standardized with chemical toxicology in mind. However, nanoparticles display several unique physicochemical properties that can interfere with or pose challenges to classical toxicity assays. Recently, some new methods and modified versions of pre-existing methods have been developed for assessing the toxicity of nanomaterials. This review is an attempt to highlight some important methods employed in nanomaterial toxicology and to provide a critical analysis of the major issues/challenges faced in this emerging field.     

Understanding and controlling the interaction of nanomaterials with proteins in a physiological environment

Nanomaterials hold promise as multifunctional diagnostic and therapeutic agents. However, the effective application of nanomaterials is hampered by limited understanding and control over their interactions with complex biological systems. When a nanomaterial enters a physiological environment, it rapidly adsorbs proteins forming what is known as the protein 'corona'. The protein corona alters the size and interfacial composition of a nanomaterial, giving it a biological identity that is distinct from its synthetic identity. The biological identity determines the physiological response including signalling, kinetics, transport, accumulation, and toxicity. The structure and composition of the protein corona depends on the synthetic identity of the nanomaterial (size, shape, and composition), the nature of the physiological environment (blood, interstitial fluid, cell cytoplasm, etc.), and the duration of exposure. In this critical review, we discuss the formation of the protein corona, its structure and composition, and its influence on the physiological response. We also present an 'adsorbome' of 125 plasma proteins that are known to associate with nanomaterials. We further describe how the protein corona is related to the synthetic identity of a nanomaterial, and highlight efforts to control protein-nanomaterial interactions. We conclude by discussing gaps in the understanding of protein-nanomaterial interactions along with strategies to fill them (167 references).     

Impact of graphene-based nanomaterials (GBNMs) on the structural and functional conformations of hepcidin peptide

Graphene-based nanomaterials (GBNMs) are widely used in various industrial and biomedical applications. GBNMs of different compositions, size and shapes are being introduced without thorough toxicity evaluation due to the unavailability of regulatory guidelines. Computational toxicity prediction methods are used by regulatory bodies to quickly assess health hazards caused by newer materials. Due to increasing demand of GBNMs in various size and functional groups in industrial and consumer based applications, rapid and reliable computational toxicity assessment methods are urgently needed. In the present work, we investigate the impact of graphene and graphene oxide nanomaterials on the structural conformations of small hepcidin peptide and compare the materials for their structural and conformational changes. Our molecular dynamics simulation studies revealed conformational changes in hepcidin due to its interaction with GBMNs, which results in a loss of its functional properties. Our results indicate that hepcidin peptide undergo severe structural deformations when superimposed on the graphene sheet in comparison to graphene oxide sheet. These observations suggest that graphene is more toxic than a graphene oxide nanosheet of similar area. Overall, this study indicates that computational methods based on structural deformation, using molecular dynamics (MD) simulations, can be used for the early evaluation of toxicity potential of novel nanomaterials.     

Proteomic profiling of protein corona formed on the surface of nanomaterial

The formation of protein coronas on nanomaterial will significantly alter the surface properties of nanomaterial in biological systems and subsequently impact biological responses including signaling, cellular uptake, transport, and toxicity etc. It is of critical importance to understand the formation of protein coronas on the surface of nanomaterial. Analytical techniques, especially mass spectrometry-based proteomics methods, are playing a key role for the qualitative and quantitative analyses of protein coronas on nanomaterial. In this review, the proteomic approaches developed for the characterization of protein coronas on various nanomaterials are introduced with the emphasis on the mass spectrometry-based proteomic strategies.     

Nanomaterials for Biomedical Applications: Production,Characterisations, Recent Trends and Difficulties

Designing of nanomaterials has now become a top-priority research goal with a view to developing specific applications in the biomedical fields. In fact, the recent trends in the literature show that there is a lack of in-depth reviews that specifically highlight the current knowledge based on the design and production of nanomaterials. Considerations of size, shape, surface charge and microstructures are important factors in this regard as they affect the performance of nanoparticles (NPs). These parameters are also found to be dependent on their synthesis methods. The characterisation techniques that have been used for the investigation of these nanomaterials are relatively different in their concepts, sample preparation methods and obtained results. Consequently, this review article aims to carry out an in-depth discussion on the recent trends on nanomaterials for biomedical engineering, with a particular emphasis on the choices of the nanomaterials, preparation methods/instruments and characterisations techniques used for designing of nanomaterials. Key applications of these nanomaterials, such as tissue regeneration, medication delivery and wound healing, are also discussed briefly. Covering this knowledge gap will result in a better understanding of the role of nanomaterial design and subsequent larger-scale applications in terms of both its potential and difficulties.     

Black Phosphorus Rediscovered: From Bulk Material to Monolayers

Phosphorus is a nonmetal with several allotropes, from the highly reactive white phosphorus to the thermodynamically stable black phosphorus (BP) with a puckered orthorhombic layered structure. The bulk form of BP was first synthesized in 1914, but received little attention until it was rediscovered in 2014 as a member of the new wave of 2D layered nanomaterials. BP can be exfoliated to a single sheet that acts as a semiconductor with a tunable direct band gap, a high carrier mobility at room temperature, and an in-plane anisotropy. The development of BP applications is hampered by surface degradation, thus efforts to achieve effective BP passivation are ongoing, such as its integration in van der Waals heterostructures. BP has been tested as a novel nanomaterial in batteries, transistors, sensors, and photonics. This Review begins with the origin of the BP story, following the path from a bulk material to modern few/single layers. The physical and chemical properties are summarized, and the state-of-the-art of BP applications highlighted.     

Design and synthesis of novel polyglycerol hybrid nanomaterials for potential applications in drug delivery systems

The synthesis of a new drug delivery system based on hybrid nanomaterials containing a β-CD core and hyperbranched PG is described. Conjugating PG branches onto β-CD not only increases its water solubility but also affects its host/guest properties deeply. It can form molecular inclusion complexes with small hydrophobic guest molecules such as ferrocene or FITC with reasonable release. In addition, the achievable payloads are significantly higher as for carriers such as hyperbranched PGs. Short-term in vitro cytotoxicity and hemocompatibility tests on L929 cell lines show that the hybrid nanomaterial is highly biocompatible. Due to their outstanding properties, β-CD-g-PG hybrid nanomaterials are introduced as promising materials for nanomedicine, e.g., for drug delivery issues.     

不同形貌纳米SnO2的可控合成及催化发光传感器

本文以碳纳米管(CNT)为模板、采用液相沉积法、通过改变煅烧温度可控合成了SnO2-CNT复合纳米材料、SnO2纳米棒、SnO2纳米粒子等3种形貌的SnO2纳米材料,研究了3种形貌的SnO2纳米材料对乙酸乙酯催化发光的影响;通过考察3种不同形貌SnO2纳米材料的纳米尺度和结构,讨论了影响纳米材料催化发光特性的因素;研究了3种不同形貌SnO2纳米材料对乙酸乙酯催化发光图谱和强度的变化,建立了3种新型、高效的不同形貌纳米催化发光传感器。     

Electrochemical detection based on nanomaterials in CE and microfluidic systems

Electrochemical detection has a great potential in microfluidic systems due to its easy miniaturization without losing analytical performance. In addition, the use of nanomaterials in electroanalysis improves sensitivity, selectivity, and reproducibility. The topic of this review is the use of nanomaterials (nanoparticles, nanotubes, graphene) in electrochemical detection for capillary electrophoresis and microfluidic systems (microchips and paper based analytical devices). This review covers from 2015 up to now and it is a continuation of our previous review, also published in Electrophoresis journal. The following aspects of the surveyed articles are mainly addressed: type of nanomaterial, protocol of working electrode preparation (composite, drop casting and others), advantages of nanomaterial employment and application field (clinical, food, environmental and home security). The use of nanomaterials is still an interesting approach to improve the analytical performance of electrochemical detection based on microfluidic devices. Along the review, readers will find new protocols for working electrode modification, new carbon nanomaterials and promising applications in the aforementioned fields.     

Toxicity of amorphous silica nanoparticles on eukaryotic cell model is determined by particle agglomeration and serum protein adsorption effects

Cell cultures form the basis of most biological assays conducted to assess the cytotoxicity of nanomaterials. Since the molecular environment of nanoparticles exerts influence on their physicochemical properties, it can have an impact on nanotoxicity. Here, toxicity of silica nanoparticles upon delivery by fluid-phase uptake is studied in a 3T3 fibroblast cell line. Based on XTT viability assay, cytotoxicity is shown to be a function of (1) particle concentration and (2) of fetal calf serum (FCS) content in the cell culture medium. Application of dynamic light scattering shows that both parameters affect particle agglomeration. The DLS experiments verify the stability of the nanoparticles in culture medium without FCS over a wide range of particle concentrations. The related toxicity can be mainly accounted for by single silica nanoparticles and small agglomerates. In contrast, agglomeration of silica nanoparticles in all FCS-containing media is observed, resulting in a decrease of the associated toxicity. This result has implications for the evaluation of the cytotoxic potential of silica nanoparticles and possibly also other nanomaterials in standard cell culture.     

Green Silver and Gold Nanoparticles: Biological Synthesis Approaches and Potentials for Biomedical Applications

The nanomaterial industry generates gigantic quantities of metal-based nanomaterials for various technological and biomedical applications; however, concomitantly, it places a massive burden on the environment by utilizing toxic chemicals for the production process and leaving hazardous waste materials behind. Moreover, the employed, often unpleasant chemicals can affect the biocompatibility of the generated particles and severely restrict their application possibilities. On these grounds, green synthetic approaches have emerged, offering eco-friendly, sustainable, nature-derived alternative production methods, thus attenuating the ecological footprint of the nanomaterial industry. In the last decade, a plethora of biological materials has been tested to probe their suitability for nanomaterial synthesis. Although most of these approaches were successful, a large body of evidence indicates that the green material or entity used for the production would substantially define the physical and chemical properties and as a consequence, the biological activities of the obtained nanomaterials. The present review provides a comprehensive collection of the most recent green methodologies, surveys the major nanoparticle characterization techniques and screens the effects triggered by the obtained nanomaterials in various living systems to give an impression on the biomedical potential of green synthesized silver and gold nanoparticles.     

A facile approach for quantifying the density of defects (edge plane sites) of carbon nanomaterials and related structures

A facile methodology based on cyclic voltammetry is presented allowing the density of defects, viz edge plane like-sites/defects of carbon nanomaterials to be readily quantified. The approach is based on the construction of carbon nanomaterial paste electrodes which is measured using cyclic voltammetry and a standard electrochemical redox probe. This protocol allows a quantitative relationship between the heterogeneous electron-transfer rate and the density of defects to be readily determined and also provides researchers with a methodology to quantify the density of defects for comparative purposes.     

Carbon Nanomaterials for Targeted Cancer Therapy Drugs: A Critical Review

Cancer represents one of the main causes of human death in developed countries. Most current therapies, unfortunately, carry a number of side effects, such as toxicity and damage to healthy cells, as well as the risk of resistance and recurrence. Therefore, cancer research is trying to develop therapeutic procedures with minimal negative consequences. The use of nanomaterial‐based systems appears to be one of them. In recent years, great progress has been made in the field using nanomaterials with high potential in biomedical applications. Carbon nanomaterials, thanks to their unique physicochemical properties, are gaining more and more popularity in cancer therapy. They are valued especially for their ability to deliver drugs or small therapeutic molecules to these cells. Through surface functionalization, they can specifically target tumor tissues, increasing the therapeutic potential and significantly reducing the adverse effects of therapy. Their potential future use could, therefore, be as vehicles for drug delivery. This review presents the latest findings of research studies using carbon nanomaterials in the treatment of various types of cancer. To carry out this study, different databases such as Web of Science, PubMed, MEDLINE and Google Scholar were employed. The findings of research studies chosen from more than 2000 viewed scientific publications from the last 15 years were compared.     

A chemical approach for cell-specific targeting of nanomaterials: small-molecule-initiated misfolding of nanoparticle corona proteins

A major challenge in nanomaterial science is to develop approaches that ensure that when administered in vivo, nanoparticles can be targeted to their requisite site of action. Herein we report the first approach that allows for cell-specific uptake of nanomaterials by a process involving reprogramming of the behavior of the ubiquitous protein corona of nanomaterials. Specifically, judicious surface modification of quantum dots with a small molecule that induces a protein-misfolding event in a component of the nanoparticle-associated protein corona renders the associated nanomaterials susceptible to cell-specific, receptor-mediated endocytosis. We see this chemical approach as a new and general method for exploiting the inescapable protein corona to target nanomaterials to specific cells.     

Functional tumor imaging based on inorganic nanomaterials

Inorganic nanomaterials have attracted substantial research interest due to their unique intrinsic physicochemical properties.We highlighted recent advances in the applications of inorganic nanoparticles regarding their imaging efficacy, focusing on tumor-imaging nanomaterials such as metal-based and carbon-based nanomaterials and quantum dots. Inorganic nanoparticles gain excellent in vivo tumor-imaging functions based on their specific characteristics of strong near-infrared optical absorption and/or X-ray attenuation capability. The specific response signals from these novel nanomaterials can be captured using a series of imaging techniques, i.e., optical coherence tomography(OCT), X-ray computed tomography(CT) imaging, two-photon luminescence(TPL), photoacoustic tomography(PAT), magnetic resonance imaging(MRI), surface-enhanced Raman scattering(SERS) and positron emission tomography(PET). In this review, we summarized the rapid development of inorganic nanomaterial applications using these analysis techniques and discussed the related safety issues of these materials.     

Natural nanomaterial as hard template for scalable synthesizing holey carbon naonsheet/nanotube with in-plane and out-of-plane pores for electrochemical energy storage

By tuning the structure of hard template kaolinite, we have achieved a template directed synthesis of holey carbon nanosheet/nanotube material. This carbon nanomaterial with in-plane and out-of-plane pores has shown promising electrochemical energy storage capacity.     

The Cytotoxicity of Layered Black Phosphorus

Black phosphorus (BP), the latest addition to the family of 2D layered materials, has attracted much interest owing to potential optoelectronics, nanoelectronics, and biomedicine applications. Little is known about its toxicity, such as whether it could be as toxic as white phosphorus. In response to the possibility of BP employment into commercial products and biomedical devices, its cytotoxicity to human lung carcinoma epithelial cells (A549) was investigated. Following a 24 h exposure of the cells with different BP concentrations, cell viability assessments were conducted using water‐soluble tetrazolium salt (WST‐8) and methylthiazolyldiphenyltetrazolium bromide (MTT) assays. The toxicological effects were found to be dose‐dependent, with BP reducing cell viabilities to 48 % (WST‐8) and 34 % (MTT) at 50 μg mL^?1 exposure. This toxicity was observed to be generally intermediate between that of graphene oxides and exfoliated transition‐metal dichalcogenides (MoS₂, WS₂, WSe₂). The relatively low toxicity paves the way to utilization of black phosphorus.