Biomineralized Manganese Oxide Nanoparticles Synergistically Relieve Tumor Hypoxia and Activate Immune Response with Radiotherapy in Non-Small Cell Lung Cancer.
Biomineralized Manganese Oxide Nanoparticles Synergistically Relieve Tumor Hypoxia and Activate Immune Response with Radiotherapy in Non-Small Cell Lung Cancer.
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DOI：
10.3390/nano12183138
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发表时间：
2022-09-10
期刊：
影响因子：
--
通讯作者：
Xie C
中科院分区：
文献类型：
--
作者：
Liu X;Kifle MT;Xie H;Xu L;Luo M;Li Y;Huang Z;Gong Y;Wu Y;Xie C
放疗（RT）目前被认为是非小细胞肺癌（NSCLC）的基本治疗方法；它可以通过促进全身免疫反应直接或间接诱导细胞死亡。然而，肿瘤缺氧、免疫抑制肿瘤微环境（immunosuppressive tumor microenvironment， TME）等因素仍是影响RT疗效的障碍。在此，我们报告了通过温和的酶促反应制备的生物矿化氧化锰纳米颗粒（Bio-MnO2 NPs）可能是通过缓解肿瘤缺氧和激活cGAS-STING途径协同增强RT和RT诱导的免疫反应的有希望的候选物。Bio-MnO2 NPs可以将内源性H2O2转化为O2，并催化活性氧的产生，从而使NSCLC细胞的放射敏感性增敏。同时，向TME释放Mn2+显著增强cGAS-STING活性，激活放射免疫应答，促进免疫原性细胞死亡，增加细胞毒性T细胞浸润。总的来说，这项工作展示了生物mno2 NPs在非小细胞肺癌中协同rt诱导的抗肿瘤免疫反应的TME逆转的巨大前景。
Radiotherapy (RT) is currently considered as an essential treatment for non-small cell lung cancer (NSCLC); it can induce cell death directly and indirectly via promoting systemic immune responses. However, there still exist obstacles that affect the efficacy of RT such as tumor hypoxia and immunosuppressive tumor microenvironment (TME). Herein, we report that the biomineralized manganese oxide nanoparticles (Bio-MnO2 NPs) prepared by mild enzymatic reaction could be a promising candidate to synergistically enhance RT and RT-induced immune responses by relieving tumor hypoxia and activating cGAS-STING pathway. Bio-MnO2 NPs could convert endogenic H2O2 to O2 and catalyze the generation of reactive oxygen species so as to sensitize the radiosensitivity of NSCLC cells. Meanwhile, the release of Mn2+ into the TME significantly enhanced the cGAS-STING activity to activate radio-immune responses, boosting immunogenic cell death and increasing cytotoxic T cell infiltration. Collectively, this work presents the great promise of TME reversal with Bio-MnO2 NPs to collaborate RT-induced antitumor immune responses in NSCLC.
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