4.8 Article

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

Journal

THERANOSTICS
Volume 13, Issue 12, Pages 4121-4137

Publisher

IVYSPRING INT PUBL
DOI: 10.7150/thno.84500

Keywords

radiation therapy; tumor microenvironment; anti -tumor immunity; immunogenic cell death

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Research aims to improve the immune response of radiation therapy (RT) by reshaping the immunosuppressive tumor microenvironment. A nanocomposite called UMP, constructed with core-shell UiO@Mn3O4, is used to reshape the TME and enhance immunogenic RT, inducing strong immunogenic cell death. This study is significant for TME reshaping and the development of cancer nanomedicine.
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.

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