Molecular characterizations of nanodiamond and related carbon-based nanomaterials in the human cell line and zebrafish models

Carbon-based nanomaterials (CBNs) have been considered as prospective and frontline materials for not only industrial but also biomedical applications. With unique chemical and physical properties including mechanical, electrical, and thermal diversity, CBNs recently attracted great attention for drug delivery system development. However, the biocompatibility of CBNs structural diversity in human beings is still obscure. Moreover, the general molecular and genetic regulations of CBNs within human cells have not been examined and compared before. In this study, it would be the first time that six different carboxylated CBNs were introduced, including nanodiamond (ND), graphene (Gra), single-wall carbon nanotube (SW), graphene quantum dot (GQD), and two fullerenes (C₆₀ and C₇₀), covering different kinds of nanostructure, from 0-dimension to 3-dimension, were compared and investigated in different systems. We characterized the CBNs, examined their cellular biocompatibility in human kidney (293T) and lung (IMR90) cells, and investigated the cell cycle regulations and cell death pathways activation mediated by CBNs. The transcriptome profile of human cells exposed to CBNs was examined, and among all, ND exposed samples exhibited diverse regulatory patterns, and therefore the related complex network-and-pathway regulations of the CBN in human cells were further analyzed. In the zebrafish embryo model, all CBNs did not influence either the survival or hatching rates of the embryos, demonstrating the great biocompatibility of CBNs. This study evidences that carboxylated CBNs with various dimensional structures exhibited different molecular modulations toward human cells, and provides novel insights into the safety evaluations of CBNs for future applications.