MMP13-responsive hydrogel microspheres for osteoarthritis treatment by precise delivery of celecoxib
作者全名：Xiang, Honglin; Zhang, Chuan; Xiong, Yongfu; Wang, Yong; Pu, Chaoyu; He, Jiangtao; Chen, Lu; Jiang, Ke; Zhao, Weikang; Yang, Hanfeng; Wang, Fan; Li, Yuling
作者地址：[Xiang, Honglin; Zhang, Chuan; Wang, Yong; Pu, Chaoyu; He, Jiangtao; Chen, Lu; Jiang, Ke; Yang, Hanfeng; Li, Yuling] North Sichuan Med Coll, Nanomed Innovat Res & Dev Transformat Inst, Dept Orthoped, Lab Biol Tissue Engn & Digital Med,Affiliated Hosp, 1 South Maoyuan Rd, Nanchong 637000, Sichuan, Peoples R China; [Wang, Fan] Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Traumatol & Orthoped, Dept Orthoped,Shanghai Key Lab Prevent & Treatment, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China; [Xiong, Yongfu] North Sichuan Med Coll, Dept Hepatobiliary Surg, Academician Expert Workstat, Affiliated Hosp, Nanchong 637600, Peoples R China; [Xiong, Yongfu] Guangxi Med Univ, Pharmaceut Coll, Nanning 530021, Guangxi, Peoples R China; [Zhao, Weikang] Chongqing Med Univ, Orthoped Lab, Dept Orthoped, Affiliated Hosp 1, 1 Youyi Rd, Chongqing 400016, Peoples R China
通信作者：Yang, HF; Li, YL (通讯作者)，North Sichuan Med Coll, Nanomed Innovat Res & Dev Transformat Inst, Dept Orthoped, Lab Biol Tissue Engn & Digital Med,Affiliated Hosp, 1 South Maoyuan Rd, Nanchong 637000, Sichuan, Peoples R China.; Wang, F (通讯作者)，Shanghai Jiao Tong Univ, Ruijin Hosp, Shanghai Inst Traumatol & Orthoped, Dept Orthoped,Shanghai Key Lab Prevent & Treatment, 197 Ruijin 2nd Rd, Shanghai 200025, Peoples R China.
来源：MATERIALS & DESIGN
ESI学科分类：MATERIALS SCIENCE
WOS号：WOS:001235721900001
JCR分区：Q1
影响因子：7.6
年份：2024
卷号：241
期号：
开始页：
结束页：
文献类型：Article
关键词：Hyaluronic acid; Hydrogel microsphere; Osteoarthritis; MMP13; MMP13 response
摘要：Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their longterm systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.
基金机构：Research Project of Health Commission of Sichuan Province [CSTB2022NSCQ-MSX0104, CSTB2022NSCQ-MSX0089]; Research Project of Nanchong Science and Technology Bureau [2023-1601]; [22SXJCQN0004]; [2022JB008]; [2023ZD002]
基金资助正文：This work is supported by the National Natural Science Foundation of China (82102578, 82102571) , Special Project for the Central Government to Guide the Development of Local Science and Technology in Sichuan Province (2023ZYD0071) , China Postdoctoral Science Foun-dation (2022M720603, 2022M710564, 2023MD734156, 2023M742361) , National Natural Science Foundation of Sichuan (24NSFSC1274) , Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX0104, CSTB2022NSCQ-MSX0089) , Research Project of Health Commission of Sichuan Province (2023-1601) , Research Project of Nanchong Science and Technology Bureau (22SXJCQN0004) , Research Project of the Affiliated Hospital of North Sichuan Medical College (2022JB008, 2023ZD002) . We would also like to acknowledge BioRender, which was used to create a Schematic dia-gram in this article.r (CSTB2022NSCQ-MSX0104, CSTB2022NSCQ-MSX0089) , Research Project of Health Commission of Sichuan Province (2023-1601) , Research Project of Nanchong Science and Technology Bureau (22SXJCQN0004) , Research Project of the Affiliated Hospital of North Sichuan Medical College (2022JB008, 2023ZD002) . We would also like to acknowledge BioRender, which was used to create a Schematic dia-gram in this article.
