Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy

Liang，Yujie1,2; Xu，Xiao2; Li，Xingfu2; Xiong，Jianyi2; Li，Biquan1; Duan，Li2; Wang，Daping2,3; Xia，Jiang1,4

2020-08-19

10.1021/acsami.0c10458

ACS Applied Materials & Interfaces   影响因子和分区

1944-8244

1944-8252

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.

chondrocytes exosome miR-140 osteoarthritis targeted delivery

SCI ; EI

英语

ESI高被引

其他

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]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000563074900012

AMER CHEMICAL SOC

20203809201945

Targeted drug delivery ; RNA ; Cell proliferation ; Glycoproteins ; Controlled drug delivery

Biological Materials and Tissue Engineering:461.2 ; Biology:461.9

2-s2.0-85089714485

Scopus

1.Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China
2.Department of Orthopedics,Shenzhen Intelligent Orthopaedics and Biomedical Innovation Platform,Guangdong Artificial Intelligence Biomedical Innovation Platform,Shenzhen Second People's Hospital,First Affiliated Hospital of Shenzhen University Health Science Center,Shenzhen,518035,China
3.Department of Biomedical Engineering,Southern University of Science and Technology,Shenzhen,518055,China
4.Center for Cell & Developmental Biology, School of Life Sciences, the Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China

Liang，Yujie,Xu，Xiao,Li，Xingfu,et al. Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy[J]. ACS Applied Materials & Interfaces,2020,12(33):36938-36947.

Liang，Yujie.,Xu，Xiao.,Li，Xingfu.,Xiong，Jianyi.,Li，Biquan.,...&Xia，Jiang.(2020).Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy.ACS Applied Materials & Interfaces,12(33),36938-36947.

Liang，Yujie,et al."Chondrocyte-Targeted MicroRNA Delivery by Engineered Exosomes toward a Cell-Free Osteoarthritis Therapy".ACS Applied Materials & Interfaces 12.33(2020):36938-36947.