LAUSR

Introduction The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy. Methods The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods (CuPW@PANI Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy. Results CuPW@PANI Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, CuPW@PANI Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo. Conclusion This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.