Synthesis and biocompatibility of two-dimensional biomaterials

Abstract Two-dimensional (2D) nanomaterials are receiving ever-increasing interests in biomedical applications owing to their special physicochemical characteristics. The ability to use this kind of 2D nanomaterials as drug delivery systems, tumor photothermal/photodynamic therapy agents, and diagnostic imaging agents give a strong incentive to research their in vitro and in vivo toxicities. In the review, the state-of-the-art progress of the fabrication, in vitro and in vivo toxicity research results of 2D nanomaterials including graphene and its derivatives, transition-metal dichalcogenides (TMDs), boron nitride nanosheets (BN), black phosphorus nanosheets (BP), metals nanosheets, g-C3N4 nanosheets, layered double hydroxide (LDH), clay nanosheets and other 2D nanomaterials were summarized. Upon discussing the design and surface modifications of 2D nanomaterials for therapeutic purpose, this review then concentrates on the biocompatibility study results of these 2D materials and discusses the influence of different parameters on their biocompatibility, both in vitro and in vivo. The in vitro compatibility mainly focuses on the upper limits of tolerance of different cell lines and genotoxicity of 2D nanomaterials while the in vivo compatibility embraces hemocompatibility, histocompatibility and neurotoxicity. Besides, typical in vitro and in vivo methods that were used for the biocompatibility assays were also summarized. Finally, some conclusions of the existing issues that need to be paid attention, and perspectives on future research directions of 2D nanomaterials were also discussed.