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

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@Mn(3)O(4) (denoted as UMP) nanocomposite is constructed for immunogenic RT via multiple strategies. Results: Reshaping the TME via Mn(3)O(4)-mediated integration of O(2) 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.