Yan Jie, Wang Guohao, Xie Lisi, Tian Hao, Li Jie, Li Bei, Sang Wei, Li Wenxi, Zhang Zhan, Dai Yunlu
Cancer Centre and Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR, 999078, China.
MoE Frontiers Science Center for Precision Oncology, University of Macau, Taipa, Macau SAR, 999078, China.
Adv Mater. 2022 Mar;34(10):e2105783. doi: 10.1002/adma.202105783. Epub 2022 Jan 31.
Radiotherapy, a mainstay of first-line cancer treatment, suffers from its high-dose radiation-induced systemic toxicity and radioresistance caused by the immunosuppressive tumor microenvironment. The synergy between radiosensitization and immunomodulation may overcome these obstacles for advanced radiotherapy. Here, the authors propose a radiosensitization cooperated with stimulator of interferon genes (STING) pathway activation strategy by fabricating a novel lanthanide-doped radiosensitizer-based metal-phenolic network, NaGdF :Nd@NaLuF @PEG-polyphenol/Mn (DSPM). The amphiphilic PEG-polyphenol successfully coordinates with NaGdF :Nd@NaLuF (radiosensitizer) and Mn via robust metal-phenolic coordination. After cell internalization, the pH-responsive disassembly of DSPM triggers the release of their payloads, wherein radiosensitizer sensitizes cancer cells to X-ray and Mn promote STING pathway activation. This radiosensitizer-based DSPM remarkably benefits dendritic cell maturation, anticancer therapeutics in primary tumors, accompanied by robust systemic immune therapeutic performance against metastatic tumors. Therefore, a powerful radiosensitization with STING pathway activation mediated immunostimulation strategy is highlighted here to optimize cancer radiotherapy.
放射疗法是一线癌症治疗的主要手段，但它存在高剂量辐射诱导的全身毒性以及由免疫抑制性肿瘤微环境导致的放射抗性问题。放射增敏与免疫调节之间的协同作用可能会克服晚期放射治疗中的这些障碍。在此，作者通过构建一种基于新型镧系元素掺杂放射增敏剂的金属-多酚网络NaGdF:Nd@NaLuF@PEG-多酚/Mn（DSPM），提出了一种与干扰素基因刺激物（STING）途径激活策略协同的放射增敏方法。两亲性PEG-多酚通过强大的金属-酚配位成功地与NaGdF:Nd@NaLuF（放射增敏剂）和Mn配位。细胞内化后，DSPM的pH响应性解体触发其载荷释放，其中放射增敏剂使癌细胞对X射线敏感，而Mn促进STING途径激活。这种基于放射增敏剂的DSPM显著促进树突状细胞成熟，对原发性肿瘤具有抗癌治疗效果，同时对转移性肿瘤具有强大的全身免疫治疗性能。因此，本文强调了一种通过STING途径激活介导的免疫刺激策略进行强大放射增敏以优化癌症放射治疗的方法。
