In vivo toxicology of carbon dots by ¹H NMR-based metabolomics

Owing to the promising applications of C-dots in biomedical engineering, concerns about their safety have drawn increasing attention recently. In this study, mice were intraperitoneally injected at different C-dot concentrations (0, 6.0, 12.0 and 24.0 mg kg^-1) once every 2 days for 30 days. A ¹H NMR-based metabolic approach supplemented with biochemical analysis and histopathology was used for the first time to explore the toxicity of C-dots in vivo. Histopathological inspection revealed that C-dots did not induce any obvious impairment in tissues. Biochemical assays showed no significant alterations of most measured biochemical parameters in tissues and serum, except for a slight reduction of the albumin level in serum as well as AChE activity in the liver and kidneys. Orthogonal signal correction-partial least squares-discriminant analysis (OSC-PLS-DA) of NMR profiles supplemented with correlation network analysis and SUS-plots disclosed that C-dots not only triggered the immune system but also disturbed the function of cell membranes as well as the normal liver clearance, indicating that the ¹H NMR based metabolomics approach provided deep insights into the toxicity of C-dots in vivo and gained an advantage over traditional toxicological means, and should be helpful for the understanding of its toxic mechanism.