Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
School of Life Sciences, Anhui Medical University, Hefei, 230011, China.
Adv Healthc Mater. 2023 Nov;12(29):e2301641. doi: 10.1002/adhm.202301641. Epub 2023 Aug 13.
Immunotherapy is considered to be an effective treatment for cancer and has drawn extensive interest. Nevertheless, the insufficient antigenicity and immunosuppressive tumor microenvironment often cause unsatisfactory therapeutic efficacy. Herein, a photo-activated reactive oxygen species (ROS) amplifying system (defined as "M-Cu-T") is developed to induce antitumor immune response by triggering a tumor-specific immunogenic pyroptosis. In M-Cu-T, M1 macrophage membrane-based vesicles are used for drug loading and tumor targeting, photosensitizers (meso-tetra(4-aminophenyl) porphyrin, TAPP) are used as a pyroptosis inducer, copper ions (Cu ) can enhance ROS-induced pyroptosis by consuming antioxidant systems in cells. As expected, the prepared M-Cu-T targets enrichment into tumor cells and cascades the generation of ROS, which further induces pyroptosis through caspase 3-mediated gasdermin E (GSDME) cleavage under laser activation. The pyroptotic cancer cells accompanying secrete related pattern molecules, induce immunogenic cell death, and activate antitumor immunity for immunotherapy. An effective tumor ablation is observed in LLC and CT26 cancer mouse models. This study provides inspiration for boosting the immunogenicity and achieving satisfactory therapeutic effects in cancer therapy.
免疫疗法被认为是癌症的一种有效治疗方法，引起了广泛的关注。然而，抗原性不足和免疫抑制的肿瘤微环境常常导致不尽如人意的治疗效果。在此，开发了一种光激活的活性氧 (ROS) 放大系统（定义为“M-Cu-T”），通过触发肿瘤特异性免疫原性细胞焦亡来诱导抗肿瘤免疫反应。在 M-Cu-T 中，M1 巨噬细胞膜囊泡用于药物装载和肿瘤靶向，光敏剂（间四（4-氨基苯基）卟啉，TAPP）用作细胞焦亡诱导剂，铜离子 (Cu ) 可以通过消耗细胞中的抗氧化系统来增强 ROS 诱导的细胞焦亡。正如预期的那样，制备的 M-Cu-T 靶向富集到肿瘤细胞中，并级联产生 ROS，在激光激活下，通过 caspase 3 介导的 GSDME 切割进一步诱导细胞焦亡。伴随细胞焦亡的癌细胞会释放相关模式分子，诱导免疫原性细胞死亡，并激活抗肿瘤免疫以进行免疫治疗。在 LLC 和 CT26 癌症小鼠模型中观察到有效的肿瘤消融。本研究为提高免疫原性和在癌症治疗中实现令人满意的治疗效果提供了启示。
