Microvesicle-inspired oxygen-delivering nanosystem potentiates radiotherapy-mediated modulation of tumor stroma and antitumor immunity.
basic_science · Level V
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- Record sourced from PubMed, PMID 36257260.
- Also identified by DOI 10.1016/j.biomaterials.2022.121855.
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Abstract
The efficacy of radiotherapy is greatly challenged by intense hypoxia, intricate stroma and suppressive immune microenvironments in tumors. Herein, we rationally designed a microvesicle-inspired oxygen-delivering polyfluorocarbon nanosystem loading DiIC18(5) and halofuginone (M-FDH) with prominent capacity of improving tumor oxygenation and intratumor distribution, synergizing radiation to disrupt tumor stroma and boost antitumor immunity for combinational cancer therapy. M-FDH produced a 10.98-fold enhancement of tumor oxygenation and caused efficient production of reactive oxygen species (ROS) upon radiation. M-FDH + X ray treatment resulted in notable DNA damages, over 90% elimination of cancer-associated fibroblasts (CAFs) and major components of extracellular matrix, significant enhancement of tumoricidal CD3<sup>+</sup>CD8<sup>+</sup> T cells, and profound elimination of suppressive immune cells in 4T1 tumors. The therapeutic benefits of M-FDH + X ray on suppressing tumor growth were confirmed in two murine tumor models. Therefore, this study provides an encouraging microvesicle-inspired strategy to target cancer cells and CAFs in tumors and synergize radiotherapy for effective cancer treatment.
Medical subject headings
- Neoplasms
- Cancer-Associated Fibroblasts