Deng Zheng, Xi Min, Zhang Cai, Wu Xirui, Li Quguang, Wang Chunjie, Fang Huapan, Sun Guanting, Zhang Yifan, Yang Guangbao, Liu Zhuang
Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, Jiangsu 215123, China.
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou, Jiangsu 215123, China.
ACS Nano. 2023 Mar 14;17(5):4495-4506. doi: 10.1021/acsnano.2c10352. Epub 2023 Feb 27.
Radiotherapy (RT), as one of the main methods in the clinical treatment of various malignant tumors, would induce systemic immunotherapeutic effects by triggering immunogenic cell death (ICD) of cancer cells. However, the antitumor immune responses produced by RT-induced ICD alone usually are not robust enough to eliminate distant tumors and thus ineffective against cancer metastases. Herein, a biomimetic mineralization method for facile synthesis of MnO nanoparticles with high anti-programmed death ligand 1 (αPDL1) encapsulation efficiency (αPDL1@MnO) is proposed to reinforce RT-induced systemic antitumor immune responses. This therapeutic nanoplatforms-mediated RT can significantly improve the killing of tumor cells and effectively evoke ICD by overcoming hypoxia-induced radio-resistance and reprogramming the immunosuppressive tumor microenvironment (TME). Furthermore, the released Mn ions from αPDL1@MnO under acidic tumor pH can activate the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway and facilitate the dendritic cells (DCs) maturation. Meanwhile, αPDL1 released from αPDL1@MnO nanoparticles would further promote the intratumoral infiltration of cytotoxic T lymphocytes (CTLs) and trigger systemic antitumor responses, resulting in a strong abscopal effect to effectively inhibit tumor metastases. Overall, the biomineralized MnO-based nanoplatforms offer a simple strategy for TME modulation and immune activation, which are promising for enhanced RT immunotherapy.
放射疗法（RT）作为各种恶性肿瘤临床治疗的主要方法之一，可通过引发癌细胞的免疫原性细胞死亡（ICD）诱导全身免疫治疗效果。然而，仅由RT诱导的ICD产生的抗肿瘤免疫反应通常不够强大，无法消除远处肿瘤，因此对癌症转移无效。在此，提出了一种仿生矿化方法，用于简便合成具有高抗程序性死亡配体1（αPDL1）封装效率的MnO纳米颗粒（αPDL1@MnO），以增强RT诱导的全身抗肿瘤免疫反应。这种治疗性纳米平台介导的RT可以通过克服缺氧诱导的放射抗性和重新编程免疫抑制性肿瘤微环境（TME），显著提高肿瘤细胞的杀伤能力并有效引发ICD。此外，在酸性肿瘤pH值下从αPDL1@MnO释放的Mn离子可以激活环磷酸鸟苷-腺苷酸合酶（cGAS）-干扰素基因刺激因子（STING）途径，并促进树突状细胞（DCs）成熟。同时，从αPDL1@MnO纳米颗粒释放的αPDL1将进一步促进细胞毒性T淋巴细胞（CTLs）的肿瘤内浸润并触发全身抗肿瘤反应，从而产生强大的远隔效应，有效抑制肿瘤转移。总体而言，生物矿化的MnO基纳米平台为TME调节和免疫激活提供了一种简单策略，有望增强RT免疫治疗效果。
