Immunogenic Radiation Therapy for Enhanced Antitumor Immunity via a Core–Shell Nanosensitizer-Mediated Immunosuppressive Tumor Microenvironment Modulation

作者：Nai-Han Huang, Xiao‐Yan Tang, Wei Meng, Ye-Hua Lai, Xuan Zhou, Xue-Zhao Yu, Wen‐Hua Zhang, Jin-Xiang Chen · 发表于：ACS Nano · 年份：2023 · DOI：10.1021/acsnano.3c04189 · 被引用次数：33 · 研究领域：Nanoplatforms for cancer theranostics、Cancer, Stress, Anesthesia, and Immune Response、Cancer Research and Treatments

Due to the immunosuppressive tumor microenvironment (TME) and weak radiation absorption, the immune response triggered by radiation therapy (RT) is limited. Herein, a core–shell nanosensitizer UiO@MnS (denoted as UM) was genuinely constructed for the amplification of RT efficacy and induction of immunogenicity via integrating MnS-reprogrammed TME with Hf-based UiO-sensitized RT. The acid-sensitive MnS would produce H 2 S under acidic TME to improve oxygenation through inhibition mitochondrial respiration and reducing metabolic oxygen consumption, leading to decreased HIF-1α expression and enhanced radiosensitization. In addition, the generated H 2 S inhibited the catalase activity to increase the H 2 O 2 level, which subsequently enhanced the Mn 2+ -mediated Fenton-like reaction, resulting in G2/M cell cycle arrest to improve the cellular sensitivity for radiation. This impressive tumor oxygenation, cell cycle arrest, and radiosensitization procedure boosted RT efficacy and resulted in strong antitumor immunogenicity. Taken together, combining the immunosuppressive TME modulation with a sensitizing radiation strategy shows great promise for magnifying immunogenic RT outputs.