基于1-MT的协同光热肿瘤免疫疗法，基于沸石咪唑酸盐框架8
Synergistic Photothermal Tumor Immunotherapy by 1-MT Based on Zeolitic Imidazolate Framework-8 with pH-High Sensitivity
影响因子:6.50000
分区:医学2区 / 药学2区 纳米科技3区
发表日期:2024
作者:
Ruijing Su, Yue Yang, Haiyan Wu, Bo Liu, Xinyuan Tian, Chaoyu Zhou, Yanxin Hu, Tianlong Liu
摘要
对肿瘤的成功免疫反应取决于各种细胞过程。因此，迫切需要构建一种熟练的纳米植物以进行免疫疗法，该纳米疗法可以同时调节参与免疫过程的各种细胞的活性。我们已经开发了具有良好的pH值敏感性的沸石咪唑酸盐框架-8（ZIF-8）公式，有利于在肿瘤部位释放药物（酸性环境）并显着改善免疫疗法。这是通过不同治疗剂的协调作用，例如光热药物多巴胺（PDA），化学剂摄影（CPT）和免疫调节剂1-甲基-D- tryptophan（1-mt）。在这项研究中。 （NPS）在体外和体内研究，并研究了PCMZ NP的分子机制通过光热化学抑制肿瘤中的分子机制。MTT和ANNEXIN V-FITC/PI双重染色凋亡测试表明，PCMZ NPS NP可以诱导4T1细胞的凋亡和PCMZ nps nec las irlaist nec las nec las nec las nec las nec last nec last nec last nec last las nec last lasts lastss pross下las均为4TSNPS下可能4TPS下。目的是在小鼠中建立单侧乳腺癌模型，并研究PCMZ NP对肿瘤生长和肿瘤抑制小鼠的影响。结果表明，PCMZ NP在体内表现出良好的加热作用，并在808 nm激光照射下有效抑制了肿瘤的生长。此外，PCMZ NP可以诱导肿瘤细胞的免疫原性死亡，促进DC的成熟，抑制IDO途径，最后将T细胞区分为细胞毒性T细胞和辅助T细胞，以便有效地激活抗肿瘤的免疫反应。免疫系统免疫反应和逃避免疫系统的刺激不足。这为侵入性癌症和复发性肿瘤提供了强大的平台。
Abstract
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.