Journal
BIOMATERIALS
Volume 302, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2023.122339
Keywords
DOX conjugate; siRNA delivery system; Blockade CD47 signal; Activate ICD effect; Chemo-immunotherapy
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This study developed a nanoassembly that efficiently reawakens T cell and macrophage-mediated anticancer activity. By downregulating CD47 expression, the nanoassembly can block antiphagocytic signals and enhance macrophage-mediated immunotherapy. Additionally, the conjugated chemotherapy drug can induce immunogenic cell death and promote T cell-mediated anticancer immune response.
Efficiently reawakening immune cells, including T cells and macrophages, to eliminate tumor cells is a promising strategy for cancer treatment, but remains a huge challenge nowadays. Herein, a nanoassembly formed by doxorubicin (DOX)-conjugated polyphosphoester (PP-(hDOX)) and CD47-targeting siRNA (siCD47) via electro-static and 7C -7C stacking interactions, termed as PP-(hDOX&siCD47), was developed to reawaken the T cell and macrophage-mediated anticancer activity. The PP-(hDOX&siCD47) could efficiently blockade antiphagocytic signal by downregulation of CD47 expression to reactive macrophage-mediated anticancer immunotherapy. Moreover, the conjugated DOX of PP-(hDOX&siCD47) can perform the chemotherapy towards tumor cells and also elicit the T cell-mediated anticancer immune response via immunogenic cell death (ICD) effect. Therefore, the PP-(hDOX&siCD47) treatment could significantly increase M1-like macrophages proportion and tumor infiltration of CD8+ T cells, while the proportions of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) were considerably reduced in tumor tissue, eventually achieving significantly tumor growth inhibition. Overall, this study provides a simple siRNA and DOX codelivery approach to simultaneously elicit the macrophage-and T cell-mediated anticancer immune response for cancer therapy.
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