Functional Immune Cell‐Derived Exosomes Engineered for the Trilogy of Radiotherapy Sensitization. Issue 23 (17th June 2022)

• Record Type: Journal Article
• Authors: Ma, Xiaotu; Yao, Meinan; Gao, Yu; Yue, Yale; Li, Yao; Zhang, Tianjiao; Nie, Guangjun; Zhao, Xiao; Liang, Xiaolong
• Is Part Of: Advanced science. Volume 9:Issue 23(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-17
• Subjects: engineered exosome -- immune microenvironment -- macrophage polarization -- radiotherapy sensitization -- tumor hypoxia; Science -- Periodicals; 505
• DOI: 10.1002/advs.202106031
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The limited efficacy of radiotherapy leads to radio‐resistance and high rates of tumor recurrence and metastasis, which is caused by tumor hypoxia, rapid DNA damage repair, and especially the suppressive immune microenvironment of tumor. Lots of immune cell‐derived exosomes can regulate antitumor immunity, but their application in enhancing radiotherapy is rarely studied. Herein, as a model of concept, M1 macrophage‐derived exosomes (M1Exos) is engineered as effective radiotherapy sensitizers, realizing the trilogy of radiotherapy sensitization: 1) M1Exos is engineered to express catalases on the inside of membrane, which can effectively relieve tumor hypoxia, and enhance DNA damage. 2) The DNA damage repair inhibitor is loaded in M1Exos to effectively inhibit DNA damage repair. 3) M1Exos can polarize M2 macrophages into M1 phenotypes, and the anti‐PD‐L1 nanobody engineered on the outside of M1Exos can relieve the immunosuppression of T cells, both ultimately leading to the remodeling of the tumor suppressive microenvironment. The trilogy of radiotherapy sensitization achieves excellent antitumor efficacy, exhibiting the good utility of engineering immune cell‐derived exosomes as radiotherapy sensitizers, inspiring the future efforts to explore different kinds of immune cell‐derived exosomes for enhanced radiotherapy. Abstract : M1 macrophage‐derived exosomes with catalase (CAT) and anti‐PD‐L1 (programmed death ligand‐1) nanobody expressed on membrane and DNA damage repair inhibitor (DDRi) encapsulated inside is engineered as effective radiotherapy sensitizers, realizing the trilogy of radiotherapy sensitization: the relief of tumor hypoxia, the inhibition of DNA damage repair, and the remodeling of tumor suppressive immune microenvironment. This work exhibits the good utility of engineering immune cell‐derived exosomes as effective radiotherapy sensitizers.