2. Academic Validation
  3. Superoxide dismutase-loaded porous polymersomes as highly efficient antioxidant nanoparticles targeting synovium for osteoarthritis therapy

Superoxide dismutase-loaded porous polymersomes as highly efficient antioxidant nanoparticles targeting synovium for osteoarthritis therapy

  • Biomaterials. 2022 Apr;283:121437. doi: 10.1016/j.biomaterials.2022.121437.
Tao Gui 1,  Lijun Luo 2,  Bonirath Chhay 3,  Leilei Zhong 4,  Yulong Wei 5,  Lutian Yao 4,  Wei Yu 4,  Jun Li 4,  Charles L Nelson 4,  Andrew Tsourkas 3,  Ling Qin 6,  Zhiliang Cheng 7
Affiliations

Affiliations

  • 1 Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, 19104, USA; Center for Joint Surgery and Sports Medicine, The First Affiliated Hospital, Jinan University, Guangzhou, China.
  • 2 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA; School of Agricultural Engineering, Jiangsu University, Jiangsu, China.
  • 3 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 4 Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 5 Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA.
  • 6 Department of Orthopaedic Surgery, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: qinling@pennmedicine.upenn.edu.
  • 7 Department of Bioengineering, University of Pennsylvania, Philadelphia, PA, 19104, USA. Electronic address: zcheng@seas.upenn.edu.
PMID: 35247635 DOI: 10.1016/j.biomaterials.2022.121437
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.

Keywords

Antioxidant nanoparticles; Osteoarthritis; Porous polymersomes; Superoxide dismutase; Synovium.

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