Fast-scan voltammetry with an ultramicroelectrode for single-cell monitoring of DNA damage: Drug evaluation and chiral nanomaterial toxicity assessment.

DNA integrity is essential for cellular function and chemotherapy response, but real-time, single-cell monitoring of DNA damage has been difficult to achieve. In this study, we constructed an electrochemical biosensor using a DNA-modified platinum nanoelectrode (PtNE/DNA) combined with fast-scan voltammetry (FSV) at 30 kV s-1 for dynamic detection of DNA damage in a single living cell. The sensing platform utilizes a ferrocene-labeled hairpin DNA probe that specifically recognizes structural damage, while the high temporal resolution and strong anti-interference capability are provided by the FSV technology. We successfully monitored real-time DNA damage in a single HeLa cell treated with chemotherapeutic agents including doxorubicin (DOX), cisplatin (CDDP), and paclitaxel (PTX). Distinct kinetic profiles were observed: DOX elicited the most rapid and severe damage, CDDP induced intermediate progression, and PTX resulted in delayed and attenuated effects. Furthermore, we revealed enantioselective cytotoxicity of chiral carbon dots (D-CDs and L-CDs), with L-CDs showing significantly higher toxicity. These results demonstrate the utility of our approach in assessing drug sensitivity and nanomaterial biocompatibility at the single-cell level, providing a valuable tool for advancing precision medicine and toxicological research.