Sulfonated cobalt phthalocyanine coupled with poly(dopamine-co-sulfobetaine methacrylate) for single-cell electrochemical monitoring of glutathione.

Accurate monitoring of intracellular glutathione (GSH) fluctuations at the single-cell level is significant to gain an in-depth understanding of related pathological events and facilitate disease diagnosis. However, conventional sensing interfaces are susceptible to nonspecific interference and surface passivation in complex biological systems, severely restricting the development of high-performance platforms for single-cell analysis. Herein, an antifouling nanoelectrochemical sensor integrating sulfonated cobalt phthalocyanine (CoPcS) and a zwitterionic poly(dopamine-co-sulfobetaine methacrylate) layer fabricated via one-step electropolymerization was developed for GSH detection. The zwitterionic sensing interface exhibited prominent anti-interference and antifouling performance in high-concentration protein media, retaining over 90% of its initial electrochemical signals after incubation with 10 mg/mL BSA for 2 h. Benefiting from the highly selective electrocatalytic capability of CoPcS and the hydration protection effect of the robust zwitterionic polymer layer, the proposed nanosensor achieved reliable electrochemical detection of GSH. The results of single-cell analysis indicated that the proposed nanosensor successfully distinguished the different GSH levels in A549 cells and HeLa cells, and accurately responded to drug-induced intracellular GSH fluctuations. This nanosensing platform provides a powerful tool for revealing cellular heterogeneity and exploring disease pathogenesis, holding great promise for biological research and clinical therapeutic applications.