作为细胞死亡的特殊模式，免疫原性细胞死亡（ICD）能激活免疫响应。光疗与化疗（CT）相结合是一种特别有效的诱导肿瘤ICD的方法，可以克服单一治疗的缺陷。本研究设计并制备了新型双刺激响应微米胶束，通过诱导ICD实现成像引导的线粒体靶向光热/光动力/化疗综合治疗。通过将生物可降解的二羧酸PGG作为骨架，将IR780与之交联，合成了双敏感性甲氧基聚乙二醇-SS-聚（L-γ-谷氨酰谷氨酰胺）-SS-IR780（mPEG-SS-PGG-SS-IR780）聚合物，并通过将PTXL封装在疏水核心中，合成了mPEG-SS-PGG-SS-IR780/紫杉醇胶束（mPEG-SS-PGG-SS-IR780/PTXL MCs）。体内外实验结果表明，这种三模式综合胶束抑制了肿瘤生长，并提高了免疫治疗的治疗效果。这种双刺激响应的mPEG-SS-PGG-SS-IR780/PTXL MCs能促进肿瘤细胞对纳米颗粒的内吞作用，同时能够促使胶束解离并加速紫杉醇的释放。考虑到线粒体对热和活性氧（ROS）的敏感性，mPEG-SS-PGG-SS-IR780/PTXL MCs通过直接靶向线粒体诱导线粒体功能障碍。此外，mPEG-SS-PGG-SS-IR780/PTXL MCs能通过成像功能发挥诊断和治疗作用。总之，本研究通过ICD在肿瘤联合治疗方面构建了一种高效的纳米平台，具有巨大潜力。© 2023年梁等人。

As the special modality of cell death, immunogenic cell death (ICD) could activate immune response. Phototherapy in combination with chemotherapy (CT) is a particularly efficient tumor ICD inducing method that could overcome the defects of monotherapies.In this study, new dual stimuli-responsive micelles were designed and prepared for imaging-guided mitochondrion-targeted photothermal/photodynamic/CT combination therapy through inducing ICD. A dual-sensitive methoxy-polyethylene glycol-SS-poly(L-γ-glutamylglutamine)-SS-IR780 (mPEG-SS-PGG-SS-IR780) polymer was synthesized by grafting IR780 with biodegradable di-carboxyl PGG as the backbone, and mPEG-SS-PGG-SS-IR780/paclitaxel micelles (mPEG-SS-PGG-SS-IR780/PTXL MCs) were synthesized by encapsulating PTXL in the hydrophobic core.In-vivo and -vitro results demonstrated that the three-mode combination micelles inhibited tumor growth and enhanced the therapeutic efficacy of immunotherapy. The dual stimuli-responsive mPEG-SS-PGG-SS-IR780/PTXL MCs were able to facilitate tumor cell endocytosis of nanoparticles. They were also capable of promoting micelles disintegration and accelerating PTXL release. The mPEG-SS-PGG-SS-IR780/PTXL MCs induced mitochondrial dysfunction by directly targeting the mitochondria, considering the thermo- and reactive oxygen species (ROS) sensitivity of the mitochondria. Furthermore, the mPEG-SS-PGG-SS-IR780/PTXL MCs could play the diagnostic and therapeutic roles via imaging capabilities.In summary, this study formulated a high-efficiency nanoscale platform with great potential in combined therapy for tumors through ICD.© 2023 Liang et al.