Functional Immune Cell‐Derived Exosomes Engineered for the Trilogy of Radiotherapy Sensitization
Open accessAbstract
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.
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After DNA damage caused by standard treatment, tumor hypoxia can drive DNA repair to allow tumor cells to continue to grow, giving rise to resistance to antitumor therapy.
“After DNA damage caused by standard treatment, tumor hypoxia can drive DNA repair to allow tumor cells to continue to grow, giving rise to resistance to antitumor therapy.”
From Hypoxia signaling in cancer: Implications for therapeutic interventions (2023) · cites this paper as [102]
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- Authors
- Ma, X., Yao, M., Gao, Y., Yue, Y., Li, Y., Zhang, T., Nie, G., Zhao, X., & Liang, X.
- Affiliations
- Chinese Academy of Sciences (CN)
- Beijing Center for Disease Prevention and Control (CN)
- Peking University Third Hospital (CN)
- Corresponding author
- Zhao, Xiao
- Liang, Xiaolong
- Venue
- Advanced Science
- Publisher
- Wiley
- Published
- 2022-06-17
- Volume
- 9
- Issue
- 23
- Pages
- e2106031-e2106031
- ISSN
- 2198-3844 (ISSN-L)
- PMC
- PMC9376809
- OpenAlex
- W4283078286
- Cited by
- 82
- References
- 59
- Citations by year
- 2026: 7 · 2025: 26 · 2024: 28 · 2023: 17 · 2022: 4
- FWCI
- 6.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Advanced Science (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (81771846)
- Peking University Third Hospital (BYSYZD2019018, jyzc2018‐02, BYSY2015023)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Radiation Therapy and Dosimetry
- Keywords
- exosomes, radiosensitization, tumor hypoxia, catalase, DNA repair inhibition, M2 macrophage polarization, tumor immune microenvironment, radioresistance (biology), tumor recurrence, metastasis
- MeSH terms
- Tumor Hypoxia, Humans, Macrophages, Neoplasms, Exosomes, Tumor Microenvironment
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