谷胱甘肽-S-转移酶(GST)是谷胱甘肽(GSH)共轭反应中的关键酶，在癌细胞中过度表达，导致顺铂失活，最终产生药物抗性。此外，许多肿瘤是免疫“冷肿瘤”，限制了免疫检查点抑制剂的应用。因此，设计了一种具有Michael加成受体抑制GST活性和顺铂失活的反应性氧化物(ROS)-响应型聚光敏剂纳米粒子(NP2)。在808nm光照射下，一方面，NP2中的Michael加成受体会与GST反应并抑制其活性，从而减少GSH共轭反应，降低GSH介导的顺铂失活作用，提高其化疗效果。另一方面，NP2+L能在前列腺肿瘤细胞中产生更多的ROS，进一步诱导二型免疫原性细胞死亡(ICD)，刺激更强的抗肿瘤免疫反应。研究发现，在808nm光照射下，NP2可以增加前列腺癌细胞表面的PD-L1表达。随后，发现NP2 +L结合PD-L1治疗可以同时增强前列腺肿瘤的化疗和光动力免疫治疗效果，为肿瘤临床多模式治疗提供了一个新的范例。 © 2023 Wiley-VCH GmbH发表的Advanced Science的作者。

Glutathione S-transferase (GST), which is a key enzyme in the conjugation reaction of glutathione (GSH), is overexpressed in cancer cells, leading to cisplatin deactivation and ultimately drug resistance. In addition, many tumors are immune "cold tumors," limiting the application of immune checkpoint inhibitors. Herein, a reactive oxygen species (ROS)-responsive polyphotosensitizer-based nanoparticle (NP2) with Michael addition acceptors inhibiting GST activity and cisplatin deactivation is designed. Under the 808 nm light irradiation, on the one hand, the Michael addition acceptor in NP2 can react with GST and inhibit its activity, thereby decreasing the GSH conjugation and reducing the GSH-mediated deactivation of cisplatin and improving its chemotherapeutic effect. On the other hand, NP2+L induces more ROS production in prostate tumor cells, which can further induce type II immunogenic cell death (ICD) and stimulate a stronger antitumor immune response. It is found that NP2 under the 808 nm light irradiation (NP2+L) can increase PD-L1 expression on the surface of prostate cancer cells. Subsequently, NP2+L combined with PD-L1 treatment is found to simultaneously enhance the efficacies of chemotherapy and photodynamic immunotherapy in prostate tumors, providing a new paradigm for the clinical multimodal treatment of tumors.© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.