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受软骨基质启发的仿生超润滑纳米球用于骨关节炎治疗

Cartilage matrix-inspired biomimetic superlubricated nanospheres for treatment of osteoarthritis.

作者信息

Chen Hao, Sun Tao, Yan Yufei, Ji Xiuling, Sun Yulong, Zhao Xin, Qi Jin, Cui Wenguo, Deng Lianfu, Zhang Hongyu

机构信息

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China; Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China; Department of Spinal Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 160 Pujian Road, Shanghai, 200120, PR China.

State Key Laboratory of Tribology, Department of Mechanical Engineering, Tsinghua University, Beijing, 100084, China.

出版信息

Biomaterials. 2020 Jun;242:119931. doi: 10.1016/j.biomaterials.2020.119931. Epub 2020 Feb 29.

DOI:10.1016/j.biomaterials.2020.119931
PMID:32145507
Abstract

The superlubrication of natural joint has been attributed to hydration lubrication of articular cartilage. Here, inspired by the structure of phosphatidylcholine lipid (a typical cartilage matrix) with the presence of zwitterionic charges, we developed superlubricated nanospheres, namely poly (2-methacryloyloxyethyl phosphorylcholine)-grafted mesoporous silica nanospheres (MSNs-NH@PMPC), via photopolymerization. The biomimetic nanospheres could enhance lubrication due to the formation of a tenacious hydration layer surrounding the zwitterionic charges of polymer brushes (PMPC), and achieve local delivery of an anti-inflammatory drug employing the nanocarriers (MSNs). The tribological and drug release tests showed improved lubrication and sustained drug release of the nanospheres. Additionally, the in vitro and in vivo tests revealed that the superlubricated drug-loaded nanospheres inhibited the development of osteoarthritis by up-regulating cartilage anabolic components and down-regulating catabolic proteases and pain-related gene. The nanospheres, with an integrated feature of both enhanced lubrication and sustained drug delivery, can be an efficient intra-articular nanomedicine for the treatment of osteoarthritis.

摘要

天然关节的超润滑作用被认为归因于关节软骨的水化润滑。在此,受具有两性离子电荷的磷脂酰胆碱脂质(一种典型的软骨基质)结构的启发,我们通过光聚合反应制备了超润滑纳米球,即聚(2-甲基丙烯酰氧乙基磷酰胆碱)接枝的介孔二氧化硅纳米球(MSNs-NH@PMPC)。这种仿生纳米球能够增强润滑作用,这是由于在聚合物刷(PMPC)的两性离子电荷周围形成了一层坚韧的水化层,并且利用纳米载体(MSNs)实现了抗炎药物的局部递送。摩擦学和药物释放测试表明,纳米球的润滑性能得到改善,药物能够持续释放。此外,体外和体内测试显示,负载药物的超润滑纳米球通过上调软骨合成成分、下调分解代谢蛋白酶和疼痛相关基因,抑制了骨关节炎的发展。这些具有增强润滑和持续药物递送综合特性 的纳米球,可成为治疗骨关节炎的一种有效的关节内纳米药物。

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