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

被引:9
作者
Wang, Zhaoyi [1 ]
Xiong, Hao [2 ,5 ]
Zhai, Zihe [1 ]
Yao, Yuejun [1 ]
Zhou, Tong [1 ]
Zhang, Haolan [1 ]
Fan, Cunyi [2 ,5 ]
Gao, Changyou [1 ,3 ,4 ]
机构
[1] Zhejiang Univ, Dept Polymer Sci & Engn, Int Res Ctr X Polymers, MOE Key Lab Macromol Synth & Functionalizat, Hangzhou 310027, Peoples R China
[2] Shanghai Jiao Tong Univ, Dept Orthoped, Affiliated Peoples Hosp 6, Shanghai 200233, Peoples R China
[3] Zhejiang Univ, Shaoxing Inst, Ctr Healthcare Mat, Shaoxing 312035, Peoples R China
[4] Zhejiang Univ, Affiliated Hosp 2, Dept Orthoped, Sch Med, Hangzhou 310009, Peoples R China
[5] Shanghai Engn Res Ctr Orthopaed Mat Innovat & Tis, Bldg 3,Langu Sci & Technol Pk,Lane 70,Haiji 6th R, Lane 201306, Shanghai, Peoples R China
关键词
reactive oxygen species; polythioketal; osteoarthritis; nanoparticles; chondroitin sulfate; MESENCHYMAL STEM-CELLS; HISTOPATHOLOGY; MACROPHAGES;
D O I
10.1007/s12274-022-4934-x
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
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-dipheny1-2-picrylhydrazyl (DPPH) radicals without toxicity to RAVV264.7 cells in vitro. With an average diameter of similar to 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.
引用
收藏
页码:2786 / 2797
页数:12
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