Superoxide dismutase-loaded porous polymersomes as highly efficient antioxidant nanoparticles targeting synovium for osteoarthritis therapy. (April 2022)

• Record Type: Journal Article
• Authors: Gui, Tao; Luo, Lijun; Chhay, Bonirath; Zhong, Leilei; Wei, Yulong; Yao, Lutian; Yu, Wei; Li, Jun; Nelson, Charles L.; Tsourkas, Andrew; Qin, Ling; Cheng, Zhiliang
• Is Part Of: Biomaterials. Volume 283(2022)
• Publication Date: 2022-04
• Subjects: Porous polymersomes -- Antioxidant nanoparticles -- Superoxide dismutase -- Synovium -- Osteoarthritis; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2022.121437
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: Oxidative stress and the reactive oxygen species (ROS) have important roles in osteoarthritis (OA) development and progression. Scavenging ROS by exogenous antioxidant enzymes could be a promising approach for OA treatment. However, the direct use of antioxidant enzymes, such as superoxide dismutase (SOD), is challenging due to a lack of effective drug delivery system to knee joints. This study utilized a highly efficient antioxidative nanoparticle based on SOD-loaded porous polymersome nanoparticles (SOD-NPs) for delivery of SOD to mouse knee joints. The resultant SOD-NPs had prolonged mouse joint retention time with predominant accumulation in synovium but not in articular cartilage. Examining human synovial explants revealed that SOD-NPs minimize oxidative damages induced by OA-like insults. Intra-articular injections of SOD-NPs in mice receiving OA surgery were effective in attenuating OA initiation and preventing its further progression. Mechanistically, SOD-NPs reduced ROS production and the synthesis of catabolic proteases in both articular cartilage and synovium. Hence, our work demonstrates the therapeutic potential of SOD-NPs and indicate that targeting synovium holds a great promise for OA therapy.