Promoting chondrogenesis by targeted delivery to the degenerating cartilage in early treatment of osteoarthritis  

作　　者：Yuxiang Fei Xiaojing Li Zhongyang Lv Zizheng Liu Ya Xie Jiaqi Chen Weitong Li Xiyu Liu Hu Guo Huan Liu Zhaofeng Zhang Xunhao Wang Jingjing Fan Chunqing Hu Xiaoyu Jin Ruiyang Jiang Nuo Xu Jiang Xia Yang Li Dongquan Shi 

机构地区：[1]Division of Sports Medicine and Adult Reconstructive Surgery,Department of Orthopedic Surgery,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing University,321 Zhongshan Road,Nanjing,210008,Jiangsu,PR China [2]State Key Laboratory of Pharmaceutical Biotechnology,Nanjing University,Nanjing,Jiangsu,PR China [3]Branch of National Clinical Research Center for Orthopedics,Sports Medicine and Rehabilitation,PR China [4]Guangdong Provincial Engineering Research Center of Molecular Imaging,Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine,The Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai,519000,Guangdong,PR China [5]Department of Orthopedics,Nanjing Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,210002,PR China [6]Department of Chemistry,The Chinese University of Hong Kong,Shatin,Hong Kong SAR China

出　　处：《Bioactive Materials》2024年第10期624-633,共10页生物活性材料（英文）

基　　金：supported by the National Natural Science Foundation of China(82325035,82172481,32271409,82071977,and 92059104);the Six Talent Peaks Project of Jiangsu Province(WSW-079);the 2018 High-Level Health Team of Zhuhai,the Innovation Project of National Orthopedics and Sports Medicine Rehabilitation Clinical Medical Research Center(2021-NCRC-CXJJ-ZH-16);the Guangdong-Hong Kong-Macao University Joint Laboratory of Interventional Medicine Foundation of Guangdong Province(2023LSYS001).Fig.1a was created by Biorender.com.

摘　　要：Osteoarthritis(OA)is a highly incident total joint degenerative disease with cartilage degeneration as the primary pathogenesis.The cartilage matrix is mainly composed of collagen,a matrix protein with a hallmark triplehelix structure,which unfolds with collagen degradation on the cartilage surface.A collagen hybridizing peptide(CHP)is a synthetic peptide that binds the denatured collagen triple helix,conferring a potential diseasetargeting possibility for early-stage OA.Here,we constructed an albumin nanoparticle(An)conjugated with CHP,loaded with a chondrogenesis-promoting small molecule drug,kartogenin(KGN).The CHP-KGN-An particle exhibited sustained release of KGN in vitro and prolonged in vivo retention selectively within the degenerated cartilage in the knee joints of model mice with early-stage OA.Compared to treatment with KGN alone,CHP-KGN-An robustly attenuated cartilage degradation,synovitis,osteophyte formation,and subchondral bone sclerosis in OA model mice and exhibited a more prominent effect on physical activity improvement and pain alleviation.Our study showcases that targeting the degenerated cartilage by collagen hybridization can remarkably promote the efficacy of small molecule drugs and may provide a novel delivery strategy for earlystage OA therapeutics.

关 键 词：Early-stage osteoarthritis Targeting therapy COLLAGEN Triple helix Albumin nanoparticle 

分 类 号：R318[医药卫生—生物医学工程]