A review of carbon nanodot bio-interactions and safety from cells to animals 2020 to 2025.

Abstract

Carbon nanodots (CNDs) are increasingly investigated for biomedical applications because of their fluorescence, ease of synthesis, and reported biocompatibility. Their expanding therapeutic and diagnostic use requires a safety assessment that keeps pace with CND development. This review examines in vitro and in vivo studies of pristine, doped, and drug-loaded CNDs across multiple species. Most in vitro studies report low toxicity in microorganisms and mammalian cells, with oxidative stress and mitochondrial dysfunction occurring mainly above 100 µg mL⁻1 and most consistently above 500 µg mL⁻1. In vivo, most undoped or biomass-derived CNDs have minimal effects on body weight, liver and kidney function, hematological parameters, and major-organ histology, with mild, transient immune responses and good tolerance across the nervous, cardiovascular, and reproductive systems. Reported toxicity is more often linked to metal doping, photothermal or ultrasonic activation, loaded drugs, or doses at the upper end of the ranges tested than to the carbon core itself. Current findings support formulation- and exposure-specific biocompatibility rather than a general safety profile. Limited evidence on long-term exposure, biodistribution, and pharmacokinetics remains the main barrier to clinical translation, and future work should emphasize standardized reporting, chronic exposure models, and comprehensive biodistribution studies to establish clinically relevant safety thresholds.  .