Abstract
The successful applications of graphene nanomaterials in nanobiotechnology and medicine as well as their effective translation into real clinical utility hinge significantly on a thorough understanding of their nanotoxicological profile. Of all aspects of biocompatibility, the hemocompatibility of graphene nanomaterials with different blood constituents in the circulatory system is one of the most important elements that needs to be well elucidated. Once administered into biological systems, graphene nanomaterials may inevitably come into contact with the surrounding plasma proteins and blood cells. Crucially, the interactions between these hematological entities and graphene nanomaterials will influence the overall efficacy of their biomedical applications. As such, a comprehensive understanding of the hemotoxicity of graphene nanomaterials is critically important. This review presents an up-to-date elucidation of the hemotoxicity of graphene nanomaterials through their interactions with blood proteins and cells, as well as offers some perspectives on the current challenges, opportunities, and future development of this important field.
Highlights
The successful experimental isolation of single-layer two-dimensional (2D) graphene in 2004 has sparked surging interests in this class of carbon-based nanomaterials.[1]. With their unique 2D structural feature and outstanding physicochemical properties,[2,3,4,5,6,7,8,9] notably exceptional electrical conductivity, outstanding thermal conductivity, excellent mechanical strength, versatile surface chemistry, and high biocompatibility, graphene and its derivatives have been actively explored for a wide range of potential applications, spanning from nanoelectronics and energy to nanobiotechnology and Contributing Editor: Susmita Bose a)Address all correspondence to this author
This review presents a broad overview on the recent advances on the hemocompatibility and hemotoxicity of graphene nanomaterials through their interactions with blood proteins and cells (Fig. 1)
It is anticipated that graphene nanomaterials with different surface functionalities will exhibit different toxicological profiles. This was shown in a recent report which investigated the in vitro hemocompatiblity of graphene oxide (GO) modified with different surface functionalities, i.e., pristine GO (p-GO), GO-COOH, and GO-PEI, with human serum albumin (HSA).[51]
Summary
The successful experimental isolation of single-layer two-dimensional (2D) graphene in 2004 has sparked surging interests in this class of carbon-based nanomaterials.[1]. This study demonstrated that the four serum proteins could adsorb on the graphene nanomaterial surface competitively to induce the formation of protein-coated graphene nanomaterial complexes, which might fundamentally change their cellular interaction pathways and, importantly, decrease their effective cytotoxicity. It is anticipated that graphene nanomaterials with different surface functionalities will exhibit different toxicological profiles This was shown in a recent report which investigated the in vitro hemocompatiblity of GO modified with different surface functionalities, i.e., p-GO, GO-COOH, and GO-PEI, with human serum albumin (HSA).[51] It was observed that both p-GO and GO-PEI induced significant toxicity on HSA upon their interactions, while HSA displayed negligible conformation change upon binding with GO-COOH. The aPTT prolongation by GO and hydrazine-rGO was considerably weaker than that of heparin-rGO, implying that heparin-rGO possessed excellent anticoagulant behavior, and different inhibitory coagulation pathways might be realized with the use of graphene nanomaterials with different surface functionalities
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