In situ synthesis of red fluorescent gold nanoclusters with enzyme-like activity for oxidative stress amplification in chemodynamic therapy

Chemodynamic therapy (CDT) has attracted tremendous interest in cancer therapy because it is independent of oxygen and photoirradiation. However, the therapeutic efficacy of CDT is restricted by insufficient H2O2 levels in tumor cells. Herein, employing endogenous GSH as a template and cationic polymeric chitosan (CS) as crosslinker and stabilizer exhibiting easy cell uptake, red luminescent gold nanoclusters (denoted CS-GSH@AuNCs) were successfully synthesized in HeLa cells. The in situ synthesized CS-GSH@AuNCs exhibited both superoxidase dismutase (SOD) and peroxidase (POD)-like activity, which could promote the production of H2O2 from superoxide anion radicals (O-2(center dot-)) and then (OH)-O-center dot. The combination of GSH elimination and H2O2 elevation boosted the generation of (OH)-O-center dot, which could trigger cancer cell apoptosis and death. The enzyme-like activity of CS-GSH@AuNCs could be effectively activated under acidic conditions, and showed a high killing effect on tumor cells but minimal toxicity to normal cells. The developed GSH consumption and (OH)-O-center dot promotion theranostic platform is an innovative route for enhanced CDT by the amplification of oxidative stress. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.