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 trip...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.展开更多
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)+1 种基金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.
文摘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.
