Understanding the potential of nanomaterials (NMs) to cross the blood–brain barrier (BBB), as a function of their physicochemical properties and subsequent behavior, fate, and adverse effect beyond that point, is vital for evaluating the neurological effects arising from their unintentional entry into the brain, which is yet to be fully explored. This is not only due to the complex nature of the brain but also the existing analytical limitations for characterization and quantification of NMs in the complex brain environment. By using a fit-for-purpose analytical workflow and an in vitro BBB model, we show that the physiochemical properties of metallic NMs influence their biotransformation in biological matrices, which in turn modulates the transport form, efficiency, amounts, and pathways of NMs through the BBB and, consequently, their neurotoxicity. The data presented here will support in silico modeling and prediction of the neurotoxicity of NMs and facilitate the tailored design of safe NMs.
drug delivery, bioimaging probes, antibacterial agents, and tissue engineering. [2] The advantage of GBMs over other nanomaterials (NMs) in biomedical application is their high specific surface area which allows high density functionalization and drug loading on both sides of the planar structure. [3] The π-conjugated system offers high capacity for GBMs to interact with various organic compounds with aromatic structures through π-π stacking during fabrication of graphene composites or for immobilization of biomolecules such as nucleic acids, peptides, antibodies, or other therapeutic substances. [4] The same properties may also raise concerns regarding the potential risk that GBMs may cause to human health through binding of key signaling molecules for example. GBMs may interact with biomolecules, changing the structure of protein or DNA or induce oxidative damage, and so on. [5] Therefore, prior to the widespread use of GBMs, it is imperative to evaluate their potential risk to environmental and human health and to establish a proactive approach for the safe design of these materials.In a recent review article, Fadeel et al. comprehensively examined the literature on the effects of GBMs on human health and the environment and gave an overview of the state-of-the-art of safety assessment of GBMs, highlighting the importance of The increasing exploitation of graphene-based materials (GBMs) is driven by their unique properties and structures, which ignite the imagination of scientists and engineers. At the same time, the very properties that make them so useful for applications lead to growing concerns regarding their potential impacts on human health and the environment. Since GBMs are inert to reaction, various attempts of surface functionalization are made to make them reactive. Herein, surface functionalization of GBMs, including those intentionally designed for specific applications, as well as those unintentionally acquired (e.g., protein corona formation) from the environment and biota, are reviewed through the lenses of nanotoxicity and design of safe materials (safe-by-design). Uptake and toxicity of functionalized GBMs and the underlying mechanisms are discussed and linked with the surface functionalization. Computational tools that can predict the interaction of GBMs behavior with their toxicity are discussed. A concise framing of current knowledge and key features of GBMs to be controlled for safe and sustainable applications are provided for the community.
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