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Co-Polymer Carrier with Dual Advantages of Cartilage-Penetrating and Targeting Improves Delivery and Efficacy of microRNA Treatment of Osteoarthritis.

Yipu ZhaoXudong DengShenxing TanJie ZhangJiangfan HanXue WangJiawei PeiHui LiXiaoni DengChong YinDachuan YinYe TianAi-Rong Qian
Published in: Advanced healthcare materials (2022)
Osteoarthritis (OA) is a debilitating joint disease affecting nearly 400 million people with no efficient etiological therapies. OA is primarily identified by cartilage destruction, and gradual degeneration of the whole joint would happen when the OA progresses. Hence, cartilage has been identified as the primary therapeutic target of OA. Unfortunately, numerous barriers block the delivery of therapeutic agents into cartilage, including avascular trait and high hardness of the extracellular matrix. Herein, a cartilage-targeting peptide (CAP) modified polyvinylamine (PVAm)- poly (lactic-co-glycolic acid) (PLGA) co-polymer (CAP-PVAm-PLGA) was designed, which could form spherical nanoparticles with the r-miR-140 (CPP-NPs). CPP-NPs possessed enhanced mechanical properties due to the introduction of PLGA to vehicle. Meanwhile, CAP endowed the cartilage targeting which facilitated CPP-NPs localization in cartilage. With such dual advantages, CPP-NPs exhibited outstanding penetrability and accumulation in cartilage even subchondral bone, and could penetrate to a depth of 1000 μm into human cartilages. The degeneration area of cartilage was reduced by 65% and synovial inflammation score by 80% in OA mice, and the microarchitecture of subchondral bone was also ameliorated. Our studies established a promising platform for therapeutic RNA delivery in OA therapy that overcame the cartilage barriers. This article is protected by copyright. All rights reserved.
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