骨关节炎
纳米医学
纳米颗粒
材料科学
纳米技术
骨吸收
软骨
活性氧
癌症研究
细胞生物学
肿瘤微环境
免疫系统
化学
医学
免疫学
生物
生物化学
病理
内科学
替代医学
解剖
作者
Mengsi Zhan,Huxiao Sun,Zhiqiang Wang,Gaoming Li,Rui Yang,Serge Mignani,Jean Pierre Majoral,Mingwu Shen,Xiangyang Shi
出处
期刊:ACS Nano
[American Chemical Society]
日期:2024-04-02
卷期号:18 (15): 10625-10641
标识
DOI:10.1021/acsnano.4c00909
摘要
Development of nanomedicines that can collaboratively scavenge reactive oxygen species (ROS) and inhibit inflammatory cytokines, along with osteogenesis promotion, is essential for efficient osteoarthritis (OA) treatment. Herein, we report the design of a ROS-responsive nanomedicine formulation based on fibronectin (FN)-coated polymer nanoparticles (NPs) loaded with azabisdimethylphoaphonate-terminated phosphorus dendrimers (G4-TBP). The constructed G4-TBP NPs-FN with a size of 268 nm are stable under physiological conditions, can be specifically taken up by macrophages through the FN-mediated targeting, and can be dissociated in the oxidative inflammatory microenvironment. The G4-TBP NPs-FN loaded with G4-TBP dendrimer having intrinsic anti-inflammatory property and FN having both anti-inflammatory and antioxidative properties display integrated functions of ROS scavenging, hypoxia attenuation, and macrophage M2 polarization, thus protecting macrophages from apoptosis and creating designed bone immune microenvironment for stem cell osteogenic differentiation. These characteristics of the G4-TBP NPs-FN lead to their effective treatment of an OA model in vivo to reduce pathological changes of joints including synovitis inhibition and cartilage matrix degradation and simultaneously promote osteogenic differentiation for bone repair. The developed nanomedicine formulation combining the advantages of both bioactive phosphorus dendrimers and FN to treat OA may be developed for immunomodulatory therapy of different inflammatory diseases.
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