Immunogenic radiation therapy for enhanced anti-tumor immunity via core-shell nanocomposite-mediated multiple strategies Article Swipe

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Immunogenic cell death Tumor microenvironment Cancer research CD8 Immune system Immunity Radiation therapy Chemistry Medicine Immunology Immunotherapy Internal medicine

Nai-Han Huang , Along Qian , Yi‐Ming Zou , Miaoli Lin , Weilun Pan , Ming Chen , Wei Meng , Wen‐Hua Zhang , Jin-Xiang Chen ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.7150/thno.84500 · OA: W4385060156

Background: Due to the immunosuppressive tumor microenvironment (TME), radiation therapy (RT)-mediated immune response is far from satisfactory. How to improve the efficacy of immunogenic RT by priming strong immunogenic cell death (ICD) is an interesting and urgent challenge. Methods: A polyacrylic acid-coated core-shell UiO@Mn3O4 (denoted as UMP) nanocomposite is constructed for immunogenic RT via multiple strategies. Results: Reshaping the TME via Mn3O4-mediated integration of O2 production, GSH depletion, ROS generation and cell cycle arrest, accompanied by Hf-based UiO-mediated radiation absorption, eventually amplifies UMP-mediated RT to induce intense ICD. With the potent ICD induction and reprogrammed tumor-associated macrophages, this synergetic strategy can promote dendritic cells maturation and CD8+ T cells infiltration, and potentiate anti-tumor immunity against primary, distant, and metastatic tumors. Conclusion: This work is expected to shed light on the immunosuppressive TME-reshaping via multiple strategies to reinforce the immunogenic RT outcome and facilitate the development of effective cancer nanomedicine.