Nitrogen and sulfur co-doped carbon nanodots in living EA.hy926 and A549 cells: oxidative stress effect and mitochondria targeting

Carbon nanodots (CNDs) have been studied in the field of biomedicine, such as drug delivery, bioimaging and theragnosis because of their superior biocompatibility and desirable optoelectronic properties. However, limited assessments on the biological effects of CNDs, particularly the effect on oxidative stress and toxicity in living cells, are not adequately addressed. In this work, a type of nitrogen, sulfur-doped carbon nanodots (N,S-CNDs), which were found to have strong antioxidant capacity in free radical scavenging in physicochemical conditions, was investigated through measuring the fluctuations of the intracellular reactive oxygen species (ROS), such as the hydrogen peroxide and superoxide anion, at different dose exposure in two types of cell lines, EA.hy926 and A549 cells. Instead of showing antioxidative capacity, the results indicate the uptake of the N,S-CNDs induces the production of intracellular ROS, thus causing oxidative stress and deleteriousness to both cell lines. The mitochondrial membrane potential of the cells was monitored upon the N,S-CNDs treatment and found to increase monotonically with the concentration of the CNDs. In addition, the confocal imaging of the cells confirms the localization of the CNDs at the mitochondria. More evidence suggests that the N,S-CNDs may stimulate ROS generation by interacting with the electron transport chain in the mitochondrial membrane due to the sulfur composite in the CNDs.