ROS-responsive PPGF nanofiber membrane as a drug delivery system for long-term drug release in attenuation of osteoarthritis.
ROS-responsive PPGF nanofiber membrane as a drug delivery system for long-term drug release in attenuation of osteoarthritis.
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ROS响应性PPGF纳米纤维膜作为药物递送系统，可长期释放药物以减轻骨关节炎
DOI：
10.1038/s41536-022-00254-3
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发表时间：
2022-11-03
影响因子：
7.2
通讯作者：
Zhao, Jinmin
中科院分区：
文献类型：
--
作者：
Wu, Jianjun;Qin, Zainen;Jiang, Xianfang;Fang, Depeng;Lu, Zhenhui;Zheng, Li;Zhao, Jinmin
过量的活性氧（ROS）是骨关节炎（OA）发生发展的主要机制之一。然而，常规注射ROS响应性药物递送系统（DDS）如纳米颗粒和水凝胶通常由于快速清除和降解或低生物利用度而不能提供有效的治疗。本研究以聚乙二醇二乙酸二乙酯（PEGDA-EDT）为ROS响应基序，还原型氧化石墨烯（rGO）为药物载体，岩藻黄素（Fx）为抗氧化抗炎剂，采用静电纺丝法制备了一种ROS响应性膜，命名为PLA/PEGDA-EDT@rGO-Fucoxanthin（PPGF）。结果表明，PPGF膜在体外对过氧化氢（H2 O2）具有持续和长期的Fx释放行为（至少66天）。PPGF对IL-1β诱导的软骨细胞具有较低的细胞毒性和灵敏的ROS反应性，通过清除活性氧和上调抗氧化酶的活性，表现出良好的抗炎和抗氧化作用。它还证明了OA进展的减弱，8周内国际骨关节炎研究协会（OARSI）评分降低了93.17%。智能ROS响应，生物可降解和生物相容性的生物膜具有巨大的潜力，关节镜下治疗OA。
Excessive reactive oxygen species (ROS) are one of the leading mechanisms in the initiation and development of osteoarthritis (OA). However, conventional injection of ROS-responsive drug delivery systems (DDSs) such as nanoparticles and hydrogels usually cannot provide effective treatment due to rapid clearance and degradation or low bioavailability. In this study, a ROS-responsive nanofiber membrane named PLA/PEGDA-EDT@rGO-Fucoxanthin (PPGF) is fabricated by electrospinning, wherein PEGDA-EDT served as the ROS-responsive motif, reduced graphene oxide (rGO) as the drug carrier and fucoxanthin (Fx) as the antioxidative and anti-inflammatory agent. The results demonstrated that the PPGF nanofiber membrane exhibited sustained and long-term Fx release behavior (at least 66 days) in response to hydrogen peroxide (H2O2) in vitro. With low cytotoxicity and smart ROS responsiveness, PPGF showed excellent anti-inflammatory and antioxidative effects on IL-1β-induced chondrocytes by potent ROS scavenging potential and upregulation of antioxidative enzymes. It also demonstrated the attenuation of OA progression with the reduced Osteoarthritis Research Society International (OARSI) score by 93.17% in 8 weeks. The smart ROS-responsive, biodegradable and biocompatible nanofiber membranes possess great potential for OA therapy under arthroscopy.
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