高浓度谷胱甘肽（GSH）和过氧化氢（H2O2）水平是肿瘤微环境（TME）中诱导不满意的抗癌治疗效果的主要障碍。将GSH耗竭增强的化学动力疗法（CDT）与光热疗法（PTT）相结合的协同癌症治疗策略已被证明是显著提高治疗效果的有前途的方法。铜磷钨酸盐被纳入聚苯胺中设计成硫酸铜掺杂的聚苯胺纳米棒（CuPW @ PANI纳米棒），通过苯胺的化学氧化剂聚合进行。评估了低长期毒性和生物相容性。进行了体内外实验以确认GSH耗竭增强的CDT / NIR-II PTT协同治疗。CuPW @ PANI纳米棒具有生物安全性和生物相容性、强NIR-II吸收和高光热转换效率（45.14％）在NIR-II生物窗口内，使其对光声成像和NIR-II PTT高度适用。此外，CuPW @ PANI纳米棒可消耗内源性GSH以破坏氧化还原平衡，并与H2O2进行类Fenton反应产生细胞毒性•OH以增强CDT。此外，NIR-II光热诱导的局部超热能加速•OH的生成，以增强CDT，从而实现高治疗效果。本研究提供了GSH耗竭增强化学动力/ NIR-II光热治疗的概念证明。© 2023 Ye等。

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.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.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.This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.© 2023 Ye et al.