Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy
Abstract
Targeted delivery to the diseased cell or tissue is the key to the successful clinical use of nucleic acid drugs. In particular, delivery of microRNA-140 (miRNA-140, miR-140) into chondrocytes across the dense, nonvascular extracellular matrix of cartilage remains a major challenge. Here, we report the chondrocyte-targeting exosomes as vehicles for the delivery of miR-140 into chondrocytes as a new treatment for osteoarthritis (OA). By fusing a chondrocyte-affinity peptide (CAP) with the lysosome-associated membrane glycoprotein 2b protein on the surface of exosomes, we acquire CAP-exosomes that can efficiently encapsulate miR-140, specifically enter, and deliver the cargo into chondrocytes in vitro. CAP-exosomes, in contrast to nontagged exosome vesicles, are retained in the joints after intra-articular injection with minimal diffusion in vivo. CAP-exosomes also deliver miR-140 to deep cartilage regions through the dense mesochondrium, inhibit cartilage-degrading proteases, and alleviate OA progression in a rat model, pointing toward a potential organelle-based, cell-free therapy of OA.
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Exosomes can be genetically engineered, chemically surface modified or enzymatically engineered to introduce peptides and proteins to enhance their targeting ability.
“In addition, exosomes can be genetically engineered, chemically surface modified or enzymatically engineered to introduce peptides and proteins to enhance their targeting ability [42, 83–86].”
From Exosome for mRNA delivery: Strategies and therapeutic applications (2024) · cites this paper as [84]
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Self-citation
- Authors
- Liang, Y., Xu, X., Li, X., Xiong, J., Li, B., Duan, L., Wang, D., & Xia, J.
- Affiliations
- Chinese University of Hong Kong (HK)
- Shenzhen University Health Science Center (CN)
- Southern University of Science and Technology (CN)
- Corresponding author
- Duan, Li
- Wang, Daping
- Xia, Jiang
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-07-30
- Volume
- 12
- Issue
- 33
- Pages
- 36938-36947
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W3045995463
- Cited by
- 391
- References
- 41
- Citations by year
- 2026: 52 · 2025: 77 · 2024: 78 · 2023: 79 · 2022: 62 · 2021: 38 · 2020: 5
- FWCI
- 14.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Research Grants Council, University Grants Committee (14306317, 14307218, AoE/M-09/12, N_CUHK422/18)
- Ministry of Science and Technology of the People's Republic of China (2018YFA0903204)
- National Natural Science Foundation of China (81772394, 81972085, 81972116)
- Natural Science Foundation of Guangdong Province (2018B0303110003)
- Chinese University of Hong Kong
- Shenzhen Science and Technology Projects (JCYJ20170306092215436, JCYJ20170413161649437, JCYJ20170817172023838, KQTD20170331100838136)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- microRNA-140, exosomes, osteoarthritis, cell-free therapy, Lamp2b, cartilage, intra-articular injection, nucleic acid drug delivery
- MeSH terms
- Animals, Cartilage, Articular, Cells, Cultured, Extracellular Matrix, Gene Expression Regulation, Humans, Male, Membrane Glycoproteins, Osteoarthritis, Peptides, Genetic Therapy, Rats, Sprague-Dawley, Gene Transfer Techniques, Chondrocytes, MicroRNAs, Rats, Exosomes, Molecular Targeted Therapy, Optical Imaging
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