N-doped carbon dots triggered the induction of ROS-mediated cytoprotective autophagy in Hepa1-6 cells

Carbon dots (CDs) are an emerging fluorescent nano-imaging probe due to their unique characteristics, such as good conductivity, carbon-based chemical composition, and photochemical stability, which sets up the potential of outperforming the classic metal-based quantum dots (QDs). It is a timely effort to proactively investigate the biocompatibility feature of CDs with a view to safely utilize this emerging nanomaterial in biological systems. In this study, we assessed the safety profile of an in-house synthesized CDs in hepatocyte-like Hepa 1-6 cells, which represents an important target organ for CDs exposure through either particle uptake and/or accumulation and elimination from primary exposure sites post particle administration. We not only demonstrated a dose- and time-dependent compromised cell viability, but also observed the induction of autophagy at high concentration (i.e. 400 μg mL-1), authenticated by the conversion of microtubule-associated protein light chain 3 (LC3)-I to LC3-II. We attributed these changes as the protective mechanism by which the cells used to compensate for CDs-induced apoptosis and cytotoxicity. The involvement of autophagy was further confirmed because the cytotoxicity profile can be increased or reduced by the use of 3-MA (autophagy inhibitor) and NAC (ROS inhibitor), respectively. Collectively, our findings revealed dose-dependent moderate cytotoxicity in Hepa 1-6 cells. Mechanistic understanding of autophagy during the cellular process revealed the homeostasis when liver cells deal with CDs as an external insult.