Engineering Radiosensitizer‐Based Metal‐Phenolic Networks Potentiate STING Pathway Activation for Advanced Radiotherapy

• Published in: Advanced materials (Weinheim) 2022-03, Vol.34 (10), p.e2105783-n/a
• Main Authors: Yan, Jie, Wang, Guohao, Xie, Lisi, Tian, Hao, Li, Jie, Li, Bei, Sang, Wei, Li, Wenxi, Zhang, Zhan, Dai, Yunlu
• Format: Article
• Language: English
• Subjects: Cancer; Humans; Immunity; Immunotherapy; Interferon; Kinases; lanthanide‐doped radiosensitizers; manganese; Materials science; metal–phenolic networks; Neodymium; Neoplasms - therapy; Payloads; Radiation dosage; Radiation therapy; Radiation-Sensitizing Agents - pharmacology; radiosensitization effects; Radiosensitizers; Robustness; stimulator of interferon genes pathways; Stimulators; Toxicity; Tumor Microenvironment; Tumors
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202105783

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, NaGdF4:Nd@NaLuF4@PEG‐polyphenol/Mn (DSPM). The amphiphilic PEG‐polyphenol successfully coordinates with NaGdF4:Nd@NaLuF4 (radiosensitizer) and Mn2+ 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 Mn2+ 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. Radiotherapy suffers from high‐dose radiation‐induced systemic toxicity and radioresistance caused by the immunosuppressive tumor microenvironment. To overcome these limitations, a novel lanthanide‐doped radiosensitizer‐based metal‐phenolic network is engineered to achieve a synergy of radiosensitization and stimulator of interferon genes pathway activation. This tactic promotes dendritic cell maturation and evokes potent systemic antitumor immunity.