Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 33, Pages 36938-36947Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c10458
Keywords
exosome; miR-140; osteoarthritis; targeted delivery; chondrocytes
Funding
- National Key R&D Program of China [2018YFA0903204]
- University Grants Committee of Hong Kong [14306317, N_CUHK422/18, 14307218, AoE/M-09/12]
- National Natural Science Foundation of China [81772394, 81972116, 81972085]
- Key Program of Natural Science Foundation of Guangdong Province [2018B0303110003]
- Shenzhen Science and Technology Projects [KQTD20170331100838136, JCYJ20170817172023838, JCYJ20170306092215436, JCYJ20170413161649437]
- CUHK RSFS grant
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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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