针对肿瘤的成功免疫反应取决于各种细胞过程。因此，迫切需要构建一个高效的免疫治疗纳米平台，可以同时调节参与免疫过程的各种细胞的活动。我们开发了沸石咪唑骨架8（ZIF-8）配方，具有良好的pH敏感性，有利于肿瘤部位（酸性环境）药物的释放，显着提高免疫治疗效果。这是通过不同治疗剂的协调作用来实现的，例如光热剂聚多巴胺 (PDA)、化疗药物喜树碱 (CPT) 和免疫调节剂 1-甲基-D-色氨酸 (1-MT)。在这项研究中，我们评估了 PDA/(CPT 1-MT) @ZIF-8 (PCMZ) 纳米粒子 (NPs) 的体外和体内抗肿瘤作用，并研究了 PCMZ NPs 通过光热化学免疫疗法抑制肿瘤的分子机制。MTT 和膜联蛋白V-FITC/PI双染凋亡试验显示PCMZ NPs可诱导4T1细胞凋亡，且在808 nm激光照射下PCMZ NPs可引起4T1细胞坏死。目的是建立小鼠单侧乳腺癌模型，并研究PCMZ NPs对荷瘤小鼠肿瘤生长和肿瘤抑制的影响。结果表明，PCMZ NPs在808 nm激光照射下表现出良好的体内加热效果，并有效抑制肿瘤生长。此外，PCMZ NPs可以诱导肿瘤细胞免疫原性死亡，促进DCs成熟，抑制IDO途径，最终将T细胞分化为细胞毒性T细胞和辅助性T细胞，从而有效激活抗肿瘤免疫反应。 PCMZ NPs由于PDA的加入而具有良好的光热转换能力，有效克服了免疫治疗中的两个主要挑战：免疫反应刺激不足和免疫系统逃避。这为对抗侵袭性癌症和复发性肿瘤提供了一个强大的平台。© 2024 Su et al.

A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT).In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy.MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response.The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.© 2024 Su et al.