Carbon nanodots (CNDs) have attracted tremendous attention since their discovery in 2004 because of their superior water solubility, biocompatibility, photoluminescence, and opto-electronic properties. As such, CNDs have been reported potentially for broad applications in biomedicine, i.e. bioimaging, biosensor, and drug delivery systems. It becomes essential to investigate the activities of CNDs in biological systems by tuning the functionalities of CNDs including compositions, surface groups and charges, etc. Specifically, this work reports some recent findings of how the structures and functions of CNDs influence the cellular uptake, subcellular location and oxidative stress effect in terms of the regulating the reactive oxygen species (ROS) in living cells. We designed and synthesized a series of CNDs from selected precursor molecules by doping different elements (e.g. nitrogen and sulfur) and the hybrids with metal oxides such as core-shell nanoparticles thus tuning their functionalities. Both the N-doped and N,S-doped CNDs demonstrate strong antioxidant capacity by scavenging free radicals in physicochemical testing, however they show opposite effect in two cell lines, EA.hy926 and A549 cells. The N-doped CNDs offer high biocompatibility as an antioxidant by scavenging ROS in the cells, while the N,S-CNDs present strong prooxidant effect by stimulating higher level ROS generation. The cellular uptake and cellular imaging studies of the CNDs in the cells indicate both CNDs mostly target the mitochondria and evidence suggests that sulfur-functionalized CNDs interfere with the electron transport chain in the mitochondrial membrane. Additionally, the hybrid core-shell CNDs@Co<sub>3</sub>O<sub>4</sub> demonstrate different behavior in cellular uptake, cytotoxicity and ROS generation in cells. These results provide evidence that tuning structure-functions of the nanoengineered CNDs is imperative to facilitate the progress for their biomedical applications.

Tuning carbon nanodots and its hybrids for cellular uptake and the oxidative stress effect

ACS Fall 2021

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