Reactive oxygen species-scavenging nanoparticles coated with chondroitin sulfate protect cartilage against osteoarthritis in vivo  

作　　者：Zhaoyi Wang Hao Xiong Zihe Zhai Yuejun Yao Tong Zhou Haolan Zhang Cunyi Fan Changyou Gao 

机构地区：[1]MOE Key Laboratory of Macromolecular Synthesis and Functionalization,International Research Center for X Polymers,Department of Polymer Science and Engineering,Zhejiang University,Hangzhou 310027,China [2]Department of Orthopedics,Shanghai Jiao Tong University Affiliated Sixth People’s Hospital,Shanghai 200233,China [3]Center for Healthcare Materials,Shaoxing Institute,Zhejiang University,Shaoxing 312035,China [4]Department of Orthopedics,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China [5]Shanghai Engineering Research Center for Orthopaedic Material Innovation and Tissue Regeneration,Building 3,Langu Science and Technology Park,Lane 70,Haiji 6th Road,Shanghai 201306,China

出　　处：《Nano Research》2023年第2期2786-2797,共12页纳米研究（英文版）

基　　金：supported by the Key research and development program of Zhejiang Province(No.2021C03113);the Natural Science Foundation of Zhejiang Province(No.LD21E030001).

摘　　要：Osteoarthritis(OA)is a prevalent chronic inflammatory disease in joints.Current interventions confront systemic toxicity and insufficient bioavailability.The unbalanced microenvironment of OA joints mainly fosters over-expressed reactive oxygen species(ROS),extracellular matrix disintegration,and apoptosis of chondrocytes.In this study,a kind of ROS-scavenging,biodegradable and drug-free nanoparticles(PP NPs)were constructed by the crosslinking of poly(propylene fumarate)(PPF)and ROS-scavenging poly(thioketal)(PTK).The high content of PTK and high crosslinking density of PPF and PTK innovatively endowed the NPs with slow degradation and prolonged ROS-elimination ability.The NPs were further surface-modified with chondroitin sulfate(CS),one of the dietary supplements for osteoarthritis.The intrinsic properties of resultant PP-CS NPs were excavated in vitro and in vivo.The PP-CS NPs could desirably consume 1,10-diphenyl-2-picrylhydrazyl(DPPH)radicals without toxicity to RAW264.7 cells in vitro.With an average diameter of~300 nm,the PP-CS NPs could be intra-articular administrated in OA rats and showed prolonged joint retention time,allowing only one injection per month.Moreover,the PP-CS NPs possessed a prolonged ROS depletion and M2 macrophage induction effect,down-regulated inflammatory cytokines,and reduced glycosaminoglycans loss.Consequently,the PP-CS NPs protected articular surface erosion,inhibited uneven cartilage matrix,and attenuated OA progression.

关 键 词：reactive oxygen species polythioketal OSTEOARTHRITIS NANOPARTICLES chondroitin sulfate 

分 类 号：R684.3[医药卫生—骨科学]