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 H_(2)O_(2) 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 H_(2)O_(2) from superoxide anion radicals (O_(2)^(·-)) and then ^(·)OH. The combination of GSH elimination and H_(2)O_(2) elevation boosted the generation of ^(·)OH, 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 promotion theranostic platform is an innovative route for enhanced CDT by the amplification of oxidative stress.