<br>缺氧和基质金属蛋白酶 13 响应水凝胶微球可缓解体内骨关节炎进展,Small

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缺氧和基质金属蛋白酶 13 响应水凝胶微球可缓解体内骨关节炎进展
Small ( IF 13.0 ) Pub Date : 2023-12-06 , DOI: 10.1002/smll.202308599
Tong Zhou ₁ , Hao Xiong ₂ , Shun-Yu Yao ₃ , Shuqin Wang ₁ , Shifen Li ₁ , Jieting Chang ₁ , Zihe Zhai ₁ , Dong-Sheng Guo ₃ , Cunyi Fan ₂ , Changyou Gao _{1,

4,

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Affiliation

骨关节炎（OA）的发生与炎症缺氧微环境密切相关。然而目前还没有关注制造用于 OA 治疗的缺氧响应平台。在此，用甲基丙烯酸酯改性的磺化 azocalix[4] 芳烃（SAC4A-MA）、甲基丙烯酸酯化透明质酸（HA-MA）和二硫醇制备了专注于缺氧发炎关节的可注射水凝胶微球系统（HAM-SA@HCQ）。通过微流体装置和光交联技术终止基质金属蛋白酶 13 (MMP-13) 敏感肽，然后通过主客体相互作用封装抗炎药物羟氯喹 (HCQ)。由于SAC4A-MA的疏水深腔、酚基单元和偶氮键，水凝胶微球表现出强大的载药能力、突出的活性氧（ROS）清除能力和特定的缺氧响应药物释放能力。在OA组织微环境中，水凝胶微球在缺氧条件下被过量的MMP-13降解并释放HCQ，与清除ROS的杯芳烃协同抑制巨噬细胞的炎症反应。 HAM-SA@HCQ注射到OA发炎关节后，可以显着减轻氧化应激，下调缺氧诱导因子1α和炎症细胞因子的表达，防止软骨被破坏。

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Hypoxia and Matrix Metalloproteinase 13-Responsive Hydrogel Microspheres Alleviate Osteoarthritis Progression In Vivo

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host–guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.

更新日期：2023-12-06

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