Lu Yingjie, Liu Yang, Xia Xiaowei, Wu Yubin, Deng Yaoge, Yu Chenqi, Yu Jianfeng, Hou Mingzhuang, Yang Huilin, Zhang Yijian, Zhu Xuesong
Department of Orthopaedics, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China.
Orthopaedic Institute, Medical College, Soochow University, Suzhou 215000, China.
Innovation (Camb). 2025 Apr 21;6(7):100913. doi: 10.1016/j.xinn.2025.100913. eCollection 2025 Jul 7.
Treating osteoarthritis (OA) presents a significant challenge due to the fact that conventional intra-articular injections only achieve superficial penetration and uncontrolled drug release. Here, the amino-modified cationic mesoporous silica nanoparticles were covalently conjugated with cartilage-targeted peptides to form a Trojan horse-like architecture for enveloping the prochondrogenic fucoidan. The hydrogel microsphere, consisting of photocurable GelMA and ChSMA, were fabricated using a microfluidic platform for cargo delivery. The cationic targeting nanoparticle-hydrogel microsphere@fucoidan (CTNM@FU) possess three-step programmable characteristics that enable responsive transport toward injured cartilage, effective penetration of the cartilage matrix and selective entry into chondrocytes, escape from lysosomes, and release of bio-activators. The impaired cartilage metabolism was significantly reversed upon co-culturing with CTNM@FU. Intra-articular administration of CTNM@FU not only mitigated cartilage degeneration but also expedited cartilage formation. Mechanistically, CTNM@FU protected cartilage by activating SIRT3, enhancing mitochondrial energy and countering aging. Collectively, a spatiotemporally guided strategy enables more precise treatments for degenerative joint disorders.
由于传统的关节内注射只能实现表面渗透和药物的非控释，因此治疗骨关节炎（OA）面临重大挑战。在此，将氨基修饰的阳离子介孔二氧化硅纳米颗粒与软骨靶向肽共价偶联，形成一种特洛伊木马样结构以包裹促软骨生成岩藻依聚糖。由光固化甲基丙烯酸明胶（GelMA）和壳聚糖甲基丙烯酸酯（ChSMA）组成的水凝胶微球通过微流控平台制备用于药物递送。阳离子靶向纳米颗粒-水凝胶微球@岩藻依聚糖（CTNM@FU）具有三步可编程特性，能够实现对损伤软骨的响应性运输、有效穿透软骨基质并选择性进入软骨细胞、从溶酶体逃逸以及释放生物激活剂。与CTNM@FU共培养后，受损的软骨代谢得到显著逆转。关节内注射CTNM@FU不仅减轻了软骨退变，还加速了软骨形成。从机制上讲，CTNM@FU通过激活SIRT3、增强线粒体能量和对抗衰老来保护软骨。总的来说，一种时空引导策略能够为退行性关节疾病提供更精确的治疗。
