Fan Yong, Niu Zexuan, Yin Li, Yao Longtao, Ding Sheyuan, Tong Yu, Wang Jiao, Hong Zheping, Chen Jihang, Zhang Qiong, Ji Lichen, Chen Jiaxin, Xia Chen, Bi Qing
Department of Sports Medicine, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, 310000, China.
Postgraduate training base Alliance of Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China.
Mater Today Bio. 2025 Apr 17;32:101778. doi: 10.1016/j.mtbio.2025.101778. eCollection 2025 Jun.
Osteoarthritis (OA) is a progressive degenerative disorder which severely threatens the quality of life of older individuals. OA progression is closely related to heightened levels of mitochondrial reactive oxygen species (mtROS). Although nanozymes have a good ROS-scavenging effect, they cannot precisely scavenge mtROS because of the immune rejection of cell membranes, lysosomal escape, and the inability of conventional nanozymes to directly target mitochondria. Dual-target nanozymes were engineered to precisely scavenge mtROS in chondrocytes. We used chondrocyte membrane-camouflaged TPP-modified hollow Prussian blue nanozymes and subsequently encapsulated these nanozymes in a hybrid glycyrrhizic acid hydrogel. The therapeutic efficacy and underlying mechanisms were assessed in vitro and in vivo. The novel nanozymes enhanced cell selectivity, immune evasion capabilities, and mitochondrial targeting. The dual-targeted nanozymes exerted a pronounced therapeutic impact on inflammatory chondrocytes, mitigated mtDNA leakage by precisely scavenging mtROS, dampened cGAS-STING-NF-κB signaling, and enhanced chondrocyte function. The hybrid hydrogels also exhibited improved therapeutic outcomes. We confirmed the beneficial effects of the nanozyme-hydrogel combination on OA progression in mice. The nanozyme-hydrogel combination can reduce precisely scavenge mtROS in chondrocytes, avoiding the leakage of mtDNA and suppressing the cGAS-STING-NF-κB signaling pathway, thereby decreasing inflammatory responses and alleviate OA progression.
骨关节炎（OA）是一种进行性退行性疾病，严重威胁老年人的生活质量。OA的进展与线粒体活性氧（mtROS）水平升高密切相关。尽管纳米酶具有良好的ROS清除作用，但由于细胞膜的免疫排斥、溶酶体逃逸以及传统纳米酶无法直接靶向线粒体，它们不能精确清除mtROS。因此设计了双靶向纳米酶来精确清除软骨细胞中的mtROS。我们使用软骨细胞膜伪装的TPP修饰的空心普鲁士蓝纳米酶，随后将这些纳米酶封装在混合甘草酸水凝胶中。在体外和体内评估了其治疗效果和潜在机制。这种新型纳米酶提高了细胞选择性、免疫逃逸能力和线粒体靶向性。双靶向纳米酶对炎性软骨细胞具有显著的治疗作用，通过精确清除mtROS减轻mtDNA泄漏，抑制cGAS-STING-NF-κB信号传导，并增强软骨细胞功能。混合水凝胶也表现出更好的治疗效果。我们证实了纳米酶-水凝胶组合对小鼠OA进展的有益作用。纳米酶-水凝胶组合可以精确清除软骨细胞中的mtROS，避免mtDNA泄漏并抑制cGAS-STING-NF-κB信号通路，从而减少炎症反应并减轻OA进展。
