Nanoassembly of doxorubicin-conjugated polyphosphoester and siRNA simultaneously elicited macrophage- and T cell- mediated anticancer immune response for cancer therapy

Dongdong Li; Ziyang Cao; Chaoran Chen; Hengyi Li; Shan He; Xurui Hou; Ming Liang; Xianzhu Yang; Jun Wang

doi:10.1016/j.biomaterials.2023.122339

Nanoassembly of doxorubicin-conjugated polyphosphoester and siRNA simultaneously elicited macrophage- and T cell- mediated anticancer immune response for cancer therapy

Biomaterials. 2023 Nov:302:122339. doi: 10.1016/j.biomaterials.2023.122339. Epub 2023 Sep 25.

Authors

Dongdong Li¹, Ziyang Cao¹, Chaoran Chen², Hengyi Li¹, Shan He³, Xurui Hou⁴, Ming Liang⁵, Xianzhu Yang⁶, Jun Wang⁷

Affiliations

¹ Department of Nephrology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, 510006, PR China.
² School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 511442, PR China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangdong Provincial Key Laboratory of Biomedical Engineering, and Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong, 510006, PR China.
³ School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 511442, PR China.
⁴ School of International Education, Beijing University of Chemical Technology, Beijing, 100029, China.
⁵ Department of Nephrology, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong, 510006, PR China. Electronic address: eyliangming@scut.edu.cn.
⁶ School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 511442, PR China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangdong Provincial Key Laboratory of Biomedical Engineering, and Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong, 510006, PR China. Electronic address: yangxz@scut.edu.cn.
⁷ School of Biomedical Sciences and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, Guangdong, 511442, PR China; National Engineering Research Center for Tissue Restoration and Reconstruction, Guangdong Provincial Key Laboratory of Biomedical Engineering, and Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, Guangdong, 510006, PR China. Electronic address: mcjwang@scut.edu.cn.

PMID: 37778054
DOI: 10.1016/j.biomaterials.2023.122339

Abstract

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 electrostatic and π-π 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.

Keywords: Activate ICD effect; Blockade CD47 signal; Chemo-immunotherapy; DOX conjugate; siRNA delivery system.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CD47 Antigen*
CD8-Positive T-Lymphocytes / metabolism
Cell Line, Tumor
Doxorubicin / pharmacology
Doxorubicin / therapeutic use
Immunity
Immunotherapy
Macrophages / metabolism
Neoplasms* / drug therapy
RNA, Small Interfering / metabolism

Substances

CD47 Antigen
RNA, Small Interfering
Doxorubicin