Zhang Shengqing, Cai Jinhong, Yao Yi, Huang Lanli, Zheng Li, Zhao Jinmin
Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Regen Biomater. 2023 Sep 1;10:rbad078. doi: 10.1093/rb/rbad078. eCollection 2023.
Excessive reactive oxygen species (ROS)-induced mitochondrial damage has impact on osteoarthritis (OA). Nanozyme mimics as natural enzyme alternatives to scavenge excessive ROS has offered a promising strategy for OA therapy. Herein, we reported a novel mitochondrial-targeting MnO/UIO-TPP nanozyme using metal-organic frameworks with loaded MnO as the enzyme-like active core combining mitochondria-targeting triphenylphosphine (TPP) groups to serve as ROS scavengers for therapy of OA. With sequential catalysis of superoxide dismutase-like, catalase (CAT)-like, and hydroxyl radical (·OH) scavenging potentials, the nanozyme can target mitochondria by crossing subcellular barriers to effectively eliminate ROS to restore mitochondrial function and inhibit inflammation and chondrocyte apoptosis. It also has favorable biocompatibility and biosafety. Based on anterior cruciate ligament transection-induced OA joint models, this mitochondrial-targeting nanozyme effectively mitigated the inflammatory response with the Pelletier score reduction of 49.9% after 8-week therapy. This study offers a prospective approach to the design of nanomedicines for ROS-related diseases.
过量的活性氧（ROS）诱导的线粒体损伤对骨关节炎（OA）有影响。纳米酶模拟物作为清除过量ROS的天然酶替代品，为OA治疗提供了一种有前景的策略。在此，我们报道了一种新型的线粒体靶向MnO/UIO-TPP纳米酶，它以负载MnO的金属有机框架作为类酶活性核心，并结合线粒体靶向三苯基膦（TPP）基团，用作OA治疗的ROS清除剂。通过超氧化物歧化酶样、过氧化氢酶（CAT）样和羟基自由基（·OH）清除潜力的顺序催化，该纳米酶可以穿过亚细胞屏障靶向线粒体，有效消除ROS以恢复线粒体功能，并抑制炎症和软骨细胞凋亡。它还具有良好的生物相容性和生物安全性。基于前交叉韧带横断诱导的OA关节模型，这种线粒体靶向纳米酶在8周治疗后有效减轻了炎症反应，Pelletier评分降低了49.9%。本研究为ROS相关疾病的纳米药物设计提供了一种前瞻性方法。
