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受滑雪板启发的响应性药物释放润滑纳米系统,用于骨关节炎治疗。

A snowboard-inspired lubricating nanosystem with responsive drug release for osteoarthritis therapy.

机构信息

Key Laboratory of Life-Organic Analysis of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, PR China; State Key Laboratory of Solidification Processing, Center of Advanced Lubrication and Seal Materials, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an 710072, PR China.

Key Laboratory of Life-Organic Analysis of Shandong Province, School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 273165, PR China.

出版信息

J Colloid Interface Sci. 2023 Sep 15;646:331-341. doi: 10.1016/j.jcis.2023.05.019. Epub 2023 May 9.

Abstract

Most of present works of osteoarthritis (OA) therapy are focusing on reducing friction and improving drug loading capacity, while little attention is paid to realizing long-time lubrication and on-demand drug release. In this study, inspired by snowboards with good solid-liquid interface lubrication, a fluorinated graphene based nanosystem with dual functions of long-time lubrication and thermal-responsive drug release was constructed for OA synergetic therapy. An aminated polyethylene glycol bridging strategy was developed to enable covalent grafting of hyaluronic acid on fluorinated graphene. This design not only greatly increased the nanosystem's biocompatibility, but also reduced the coefficient of friction (COF) by 83.3 % compared to HO. The nanosystem showed long-time and steady aqueous lubrication behavior even after more than 24,000 times of friction tests, and a low COF of 0.13 was obtained with over 90% wear volume reduction. Diclofenac sodium was controllably loaded and sustained drug release was tuned by near-infrared light. Moreover, anti-inflammation results showed that the nanosystem had good protective effect on inhibiting OA deterioration, which could up-regulate cartilage anabolic genes of Col2α and aggrecan while down-regulating catabolic proteases genes of TAC1 and MMP1. This work constructs a novel dual-functional nanosystem that realizes friction and wear reduction with long lubrication life, and shows thermal-responsive on-demand drug release with good synergistic therapeutic effect of OA.

摘要

目前大多数骨关节炎 (OA) 治疗方法都集中在减少摩擦和提高药物载药量上,而很少关注实现长时间润滑和按需药物释放。在这项研究中,受具有良好固液界面润滑性能的滑雪板的启发,构建了一种具有长时间润滑和热响应药物释放双重功能的氟化石墨烯基纳米系统,用于 OA 协同治疗。开发了一种氨基化聚乙二醇桥接策略,以使透明质酸能够在氟化石墨烯上进行共价接枝。与 HO 相比,该设计不仅大大提高了纳米系统的生物相容性,而且还将摩擦系数 (COF) 降低了 83.3%。该纳米系统即使经过超过 24000 次摩擦测试,仍具有长时间和稳定的水润滑行为,并且在超过 90%的磨损体积减少的情况下,获得了 0.13 的低 COF。双氯芬酸钠被可控负载,近红外光可调节药物释放。此外,抗炎结果表明,纳米系统对抑制 OA 恶化具有良好的保护作用,它可以上调软骨合成基因 Col2α 和聚集蛋白聚糖,同时下调分解代谢蛋白酶基因 TAC1 和 MMP1。这项工作构建了一种新型的双重功能纳米系统,实现了具有长润滑寿命的摩擦和磨损减少,并且具有热响应按需药物释放功能,对 OA 具有良好的协同治疗效果。

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