Mild Binding of Protein to C2N Monolayer Reveals Its Suitable Biocompatibility

The development of biocompatible nanomaterials for smart drug delivery and bioimaging has attracted great interest in recent years in biomedical fields. Here, the interaction between the recently reported nitrogenated graphene (C₂N) and a prototypical protein (villin headpiece HP35) utilizing atomistic molecular dynamics simulations is studied. The simulations reveal that HP35 can form a stable binding with the C₂N monolayer. Although the C₂N–HP35 attractive interactions are constantly preserved, the binding strength between C₂N and the protein is mild and does not cause significant distortion in the protein's structural integrity. This intrinsic biofriendly property of native C₂N is distinct from several widely studied nanomaterials, such as graphene, carbon nanotubes, and MoS₂, which can induce severe protein denaturation. Interestingly, once the protein is adsorbed onto C₂N surface, its transverse migration is highly restricted at the binding sites. This restriction is orchestrated by C₂N's periodic porous structure with negatively charged “holes,” where the basic residues—such as lysine—can form stable interactions, thus functioning as “anchor points” in confining the protein displacement. It is suggested that the mild, immobilized protein attraction and biofriendly aspects of C₂N would make it a prospective candidate in bio‐ and medical‐related applications.     

Decoupling the Direct and Indirect Biological Effects of ZnO Nanoparticles Using a Communicative Dual Cell‐Type Tissue Construct

While matter at the nanoscale can be manipulated, the knowledge of the interactions between these nanoproducts and the biological systems remained relatively laggard. Current nanobiology study is rooted on in vitro study using conventional 2D cell culture model. A typical study employs monolayer cell culture that simplifies the real context of which to measure any nanomaterial effect; unfortunately, this simplification also demonstrated the limitations of 2D cell culture in predicting the actual biological response of some tissues. In fact, some of the characteristics of tissue such as spatial arrangement of cells and cell–cell interaction, which are simplified in 2D cell culture model, play important roles in how cells respond to a stimulus. To more accurately recapitulate the features and microenvironment of tissue for nanotoxicity assessments, an improved organotypic‐like in vitro multicell culture system to mimic the kidney endoepithelial bilayer is introduced. Results showed that important nano‐related parameters such as the diffusion, direct and indirect toxic effects of ZnO nanoparticles can be studied by combining this endoepithelial bilayer tissue model and traditional monolayer culture setting.     

Nanoparticle Drug Delivery Can Reduce the Hepatotoxicity of Therapeutic Cargo

Hepatotoxicity is a key concern in the clinical translation of nanotherapeutics because preclinical studies have consistently shown that nanotherapeutics accumulates extensively in the liver. However, clinical‐stage nanotherapeutics have not shown increased hepatotoxicity. Factors that can contribute to the hepatotoxicity of nanotherapeutics beyond the intrinsic hepatotoxicity of nanoparticles (NPs) are poorly understood. Because of this knowledge gap, clinical translation efforts have avoided hepatotoxic molecules. By examining the hepatotoxicity of nanoformulations of known hepatotoxic compounds, it is demonstrated that nanotherapeutics are associated with lower hepatotoxicity than their small‐molecule counterparts. It is also found that the reduced hepatotoxicity is related to the uptake of nanotherapeutics by macrophages in the liver. These findings can facilitate further development and clinical translation of nanotherapeutics.     

Aquatic Toxicity Effects and Risk Assessment of ‘Form Specific’ Product-Released Engineered Nanomaterials

The study investigated the toxicity effects of ‘form specific’ engineered nanomaterials (ENMs) and ions released from nano-enabled products (NEPs), namely sunscreens, sanitisers, body creams and socks on Pseudokirchneriella subcapitata, Spirodela polyrhiza, and Daphnia magna. Additionally, risk estimation emanating from the exposures was undertaken. The ENMs and the ions released from the products both contributed to the effects to varying extents, with neither being a uniform principal toxicity agent across the exposures; however, the effects were either synergistic or antagonistic. D. magna and S. polyrhiza were the most sensitive and least sensitive test organisms, respectively. The most toxic effects were from ENMs and ions released from sanitisers and sunscreens, whereas body creams and sock counterparts caused negligible effects. The internalisation of the ENMs from the sunscreens could not be established; only adsorption on the biota was evident. It was established that ENMs and ions released from products pose no imminent risk to ecosystems; instead, small to significant adverse effects are expected in the worst-case exposure scenario. The study demonstrates that while ENMs from products may not be considered to pose an imminent risk, increasing nanotechnology commercialization may increase their environmental exposure and risk potential; therefore, priority exposure cases need to be examined.     

High‐Sensitivity Real‐Time Analysis of Nanoparticle Toxicity in Green Fluorescent Protein‐Expressing Zebrafish

Gold nanoparticles (AuNP) show great potential for diagnostic and therapeutic application in humans. A great number of studies have tested the cytotoxicity of AuNP using cell culture. There is, however, an urgent need to test AuNP in vertebrate animal models that interrogate biodistribution and complex biological traits like organ development, whole body metabolism, and cognitive function. The sheer number of different compounds precludes the use of small rodent model for initial screening. The extended fish embryo test (FET) is used here to bridge the gap between cell culture and small animal models. A study on the toxicity of ultrasmall AuNP in wild type and transgenic zebrafish is presented. FET faithfully reproduce all important findings of a previous study in HeLa cells and add new important information on teratogenicity and hepatotoxicity that could not be gained from studying cultured cells.     

Fibroblasts Cultured on Nanowires Exhibit Low Motility,Impaired Cell Division,and DNA Damage

Nanowires are commonly used as tools for interfacing living cells, acting as biomolecule‐delivery vectors or electrodes. It is generally assumed that the small size of the nanowires ensures a minimal cellular perturbation, yet the effects of nanowires on cell migration and proliferation remain largely unknown. Fibroblast behaviour on vertical nanowire arrays is investigated, and it is shown that cell motility and proliferation rate are reduced on nanowires. Fibroblasts cultured on long nanowires exhibit failed cell division, DNA damage, increased ROS content and respiration. Using focused ion beam milling and scanning electron microscopy, highly curved but intact nuclear membranes are observed, showing no direct contact between the nanowires and the DNA. The nanowires possibly induce cellular stress and high respiration rates, which trigger the formation of ROS, which in turn results in DNA damage. These results are important guidelines to the design and interpretation of experiments involving nanowire‐based transfection and electrical characterization of living cells.     

Nanomaterial Transformation in the Soil–Plant System: Implications for Food Safety and Application in Agriculture

Engineered nanomaterials (ENMs) have huge potential for improving use efficiency of agrochemicals, crop production, and soil health; however, the behavior and fate of ENMs and the potential for negative long‐term impacts to agroecosystems remain largely unknown. In particular, there is a lack of clear understanding of the transformation of ENMs in both soil and plant compartments. The transformation can be physical, chemical, and/or biological, and may occur in soil, at the plant interface, and/or inside the plant. Due to these highly dynamic processes, ENMs may acquire new properties distinct from their original profile; as such, the behavior, fate, and biological effects may also differ significantly. Several essential questions in terms of ENMs transformation are discussed, including the drivers and locations of ENM transformation in the soil–plant system and the effects of ENM transformation on analyte uptake, translocation, and toxicity. The main knowledge gaps in this area are highlighted and future research needs are outlined so as to ensure sustainable nanoenabled agricultural applications.     

Toxico‐Metabolomics of Engineered Nanomaterials: Progress and Challenges

Nanoscale matter has unique attributes that potentiate their widespread application from biomedicine, engineering, food, cosmetics, sensing, to energy. Due to the rapid industrialization of engineered nanomaterials (ENMs) as a result of increasing consumer interests, more ENMs will be released into the environment, greatly increasing the probability of their contact with humans. Once these ENMs enter the human body or an ecosystem, they may initiate various biochemical responses in unprecedented ways, thus raising important concerns in regard to their effects on human health and the ecosystem. Here, the shifts in the intricate metabolic pathways instigated by ENMs are highlighted and those altered metabolic changes are extrapolated for the elucidation of environmental health and risk assessment. Furthermore, the toxico‐metabolomics knowledge of ENMs provides the opportunity to design novel nanomedicine with high efficacies by capitalizing on their abilities to rewire metabolic networks for the treatment of diseases.     

Effects of Nanotoxicity on Female Reproductivity and Fetal Development in Animal Models

The extensive application of nanomaterials in industry, medicine and consumer products has raised concerns about their potential toxicity. The female population is particularly vulnerable and deserves special attention because toxicity in this group may impact both female reproductivity and fetal development. Mouse and zebrafish models each have their own unique features and studies using these models to examine the potential toxicity of various nanoparticles are compared and summarized in this review. Several nanoparticles exhibit detrimental effects on female reproductivity as well as fetal development, and these adverse effects are related to nanoparticle composition, surface modification, dose, exposure route and animal species. Limited studies on the mechanisms of nanotoxicity are also documented and reviewed herein.