Responsive Exosome Nano-bioconjugates for Synergistic Cancer Therapy
Abstract
Exosomes hold great potential in therapeutic development. However, native exosomes usually induce insufficient effects in vivo and simply act as drug delivery vehicles. Herein, we synthesize responsive exosome nano-bioconjugates for cancer therapy. Azide-modified exosomes derived from M1 macrophages are conjugated with dibenzocyclooctyne-modified antibodies of CD47 and SIRPα (aCD47 and aSIRPα) through pH-sensitive linkers. After systemic administration, the nano-bioconjugates can actively target tumors through the specific recognition between aCD47 and CD47 on the tumor cell surface. In the acidic tumor microenvironment, the benzoic-imine bonds of the nano-bioconjugates are cleaved to release aSIRPα and aCD47 that can, respectively, block SIRPα on macrophages and CD47, leading to abolished "don't eat me" signaling and improved phagocytosis of macrophages. Meanwhile, the native M1 exosomes effectively reprogram the macrophages from pro-tumoral M2 to anti-tumoral M1.
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Native M1 exosomes efficiently reprogram macrophages from pro-tumor M2 to anti-tumor M1.
“Meanwhile, native M1 exosomes efficiently reprogram macrophages from pro-tumor M2 to anti-tumor M1 [44].”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [44]
Exosome nano-protein bioconjugates could specifically bind with cancer by recognition of CD47.
“Their result showed that the nano-bioconjugates could specifically bind with cancer by recognition of CD47.”
From The Therapeutic Potential and Clinical Significance of Exosomes as Carriers of Drug Delivery System (2022) · cites this paper as [44]
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- Authors
- Nie, W., Wu, G., Zhang, J., Huang, L., Ding, J., Jiang, A., Zhang, Y., Liu, Y., Li, J., Pu, K., & Xie, H.
- Affiliations
- Beijing Institute of Technology (CN)
- Chinese Academy of Sciences (CN)
- School of Chemical and Biomedical Engineering Nanyang Technological University 70 Nanyang Drive Singapore 637457 Singapore
- Nanyang Technological University (SG)
- School of Life Science Beijing Institute of Technology Beijing 100081 P. R. China
- Corresponding author
- Pu, Kanyi
- ORCID
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2019-12-18
- Volume
- 59
- Issue
- 5
- Pages
- 2018-2022
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2991079475
- Cited by
- 376
- References
- 56
- Citations by year
- 2026: 39 · 2025: 52 · 2024: 69 · 2023: 71 · 2022: 65 · 2021: 52 · 2020: 28
- FWCI
- 11.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- DR-NTU (Nanyang Technological University) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- exosomes, cancer therapy, CD47, SIRPα, M1 macrophages, macrophage reprogramming, tumor microenvironment, tumor targeting, phagocytosis, macrophage polarization
- MeSH terms
- Humans, Immunotherapy, Neoplasms, Nanotechnology, Exosomes
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