Reversing the immunosuppressive microenvironment with reduced redox level by microwave-chemo-immunostimulant Ce-Mn MOF for improved immunotherapy.
Reversing the immunosuppressive microenvironment with reduced redox level by microwave-chemo-immunostimulant Ce-Mn MOF for improved immunotherapy.
复制标题
通过微波 - 化学 - 免疫刺激剂铈 - 锰金属 - 有机框架（Ce - Mn MOF）降低氧化还原水平来逆转免疫抑制微环境以改善免疫治疗。
DOI：
10.1186/s12951-022-01699-w
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发表时间：
2022-12-03
影响因子：
10.2
通讯作者：
Meng, Xianwei
中科院分区：
文献类型：
--
作者：
Zeng, Zhiheng;Fu, Changhui;Sun, Xiaohan;Niu, Meng;Ren, Xiangling;Tan, Longfei;Wu, Qiong;Huang, Zhongbing;Meng, Xianwei
关键词：
逆转肿瘤内免疫抑制的微环境(TME)被广泛认为是改善免疫治疗的有效策略。特别是，TME中的氧化还原平衡需要很好地控制，因为它在调节各种细胞的功能方面发挥着关键作用，包括癌细胞和免疫抑制细胞。在这里，我们提出了一个有效的策略来重塑氧化还原动态平衡，以逆转免疫抑制的TME。具体地说，我们开发了一种微波化学免疫刺激剂CMMCP，通过同时减少TME中的活性氧(ROS)和谷胱甘肽(GSH)，并提高TME中的氧(O2)水平来促进肿瘤-T细胞的渗透。通过将化疗药物顺铂负载到包覆多巴胺的双金属Ce-Mn MOF纳米粒子中，设计了CMMCP。Ce-Mn MOF纳米粒子可以有效地提高微波辐射下ROS的催化分解为O2的能力，从而克服缺氧和限制ROS的产生。此外，Ce-Mn MOF纳米颗粒的氧化还原反应降低了TME中细胞内GSH的活性。重新编程的TME不仅促进了顺铂和微波热疗诱导的免疫原性细胞死亡(ICD)，而且引起了亲肿瘤的M2型巨噬细胞向抗肿瘤的M1型巨噬细胞的极化。我们的体内实验结果表明，微波-化学-免疫刺激剂CMMCP显著增强了T细胞的浸润，从而改善了抗肿瘤效果。这项研究为局部治疗后的全身抗肿瘤效应提供了一种简单、安全和有效的策略。网上版载有补充材料，可在10.1186/s12951-022-01699-w查阅。
Reversing the immunosuppressive tumor microenvironment (TME) in the tumor is widely deemed to be an effective strategy to improve immune therapy. In particular, the redox balance in TME needs to be well controlled due to its critical role in mediating the functions of various cells, including cancer cells and immune-suppressive cells. Here, we propose an efficient strategy to reshape the redox homeostasis to reverse immunosuppressive TME. Specifically, we developed a microwave-chemo-immunostimulant CMMCP to promote the infiltration of the tumor-T cells by simultaneously reducing the reactive oxygen species (ROS) and glutathione (GSH) and improving the oxygen (O2) levels in TME. The CMMCP was designed by loading chemotherapy drugs cisplatin into the bimetallic Ce–Mn MOF nanoparticles coated with polydopamine. The Ce–Mn MOF nanoparticles can effectively improve the catalytic decomposition of ROS into O2 under microwave irradiation, resulting in overcoming hypoxia and limited ROS generation. Besides, the activity of intracellular GSH in TME was reduced by the redox reaction with Ce–Mn MOF nanoparticles. The reprogrammed TME not only boosts the immunogenic cell death (ICD) induced by cisplatin and microwave hyperthermia but also gives rise to the polarization of pro-tumor M2-type macrophages to the anti-tumor M1-type ones. Our in vivo experimental results demonstrate that the microwave-chemo-immunostimulant CMMCP significantly enhances the T cell infiltration and thus improves the antitumor effect. This study presents an easy, safe, and effective strategy for a whole-body antitumor effect after local treatment. The online version contains supplementary material available at 10.1186/s12951-022-01699-w.
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