International Journal of Nanomedicine (Nov 2022)

Magnetically Guided Intracartilaginous Delivery of Kartogenin Improves Stem Cell-Targeted Degenerative Arthritis Therapy

  • Jiang Z,
  • Zhang Z,
  • Li S,
  • Lin S,
  • Yuan H

Journal volume & issue
Vol. Volume 17
pp. 5511 – 5524

Abstract

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Zengxin Jiang,1,* Zeng Zhang,1,* Shuo Li,2,* Sen Lin,3 Hengfeng Yuan1 1Department of Orthopaedics, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, People’s Republic of China; 2Department of Joint Bone Disease Surgery, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China; 3National Engineering Research Center, East China University of Science and Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sen Lin; Hengfeng Yuan, Email [email protected]; [email protected]: Degenerative joint disease or osteoarthritis (OA) is a leading cause of disability worldwide. Intra-articular injection is the mainstay nonsurgical treatment for OA. However, dense cartilage and a lack of vasculature often limit the ability of drugs to reach cell or tissue targets at the concentrations necessary to elicit the desired biological response. Kartogenin (KGN), a small molecular compound, possesses a strong capacity to promote chondrogenic differentiation of mesenchymal stem cells (MSCs). However, the rapid clearance of KGN from the intra-articular cavity limits its feasibility.Materials and Methods: We constructed a magnetically guided biodegradable nanocarrier system (MNP) which enabled intracartilaginous delivery of KGN to promote chondrogenic differentiation by MSCs embedded within the articular matrix. Moreover, in preclinical models of OA, KGN-loaded MNPs exhibited increased tissue penetration and retention within the joint matrix under external magnetic guidance.Results: Histological examination showed that compared with KGN alone, KGN-loaded MNPs enhanced chondrogenic differentiation and improved the structural integrity of both articular cartilage and subchondral bone.Conclusion: This study demonstrates a practical method for intracartilaginous delivery using engineered nanocarriers, thus providing a new strategy to improve the efficacy of molecular therapeutic agents in the treatment of OA.Graphical Abstract: Keywords: osteoarthritis, kartogenin, magnetic nanoparticles, intracartilaginous

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