Zhejiang Chinese Medical University, Hangzhou 310000, China.
Department of Orthopaedics, Jiaxing Key Laboratory of Basic Research and Clinical Translation on Orthopedic Biomaterials, The Second Affiliated Hospital of Jiaxing University, 1518 North Huancheng Road, Jiaxing 314000, P. R. China.
ACS Appl Mater Interfaces. 2022 Sep 14;14(36):40711-40723. doi: 10.1021/acsami.2c12703. Epub 2022 Sep 5.
Clinically, intra-articular administration can hardly achieve the truly targeted therapy, and the drugs are usually insufficient to show local and long-term therapeutic effects because of their rapid clearance. Herein, inspired by the phenomenon that bees track the scent of flowers to collect nectar, we developed cartilage-targeting hydrogel microspheres with reactive oxygen species (ROS)-responsive ability via combining the microfluidic method and photopolymerization processes to integrate cartilage-targeting peptides and ROS-responsive nanoparticles in the hydrogel matrix. The hydrogel microspheres with cartilage-targeting properties promoted better retention in the joint cavity and enhanced cellular uptake of the nanoparticles. Moreover, the ROS-responsive nanoparticles could react with osteoarthritis (OA)-induced intracellular ROS, resulting in the depolymerization of nanoparticles, which could not only eliminate excess ROS and reduce inflammation but also promote the release of dexamethasone (Dex) and kartogenin (KGN) , realizing effective OA therapy. It was demonstrated that this hydrogel microsphere showed favorable ROS-responsive ability and enhanced chondrogenic differentiation as well as the downregulation of pro-inflammatory factors . Additionally, the hydrogel microspheres, similar to bees, could target and effectively repair cartilage in the OA model. Thus, the injectable hydrogel microspheres exerted an excellent potential to repair OA and may also provide an effective avenue for inflammatory bowel disease therapy.
临床上，关节内给药很难实现真正的靶向治疗，由于药物快速清除，药物通常不足以显示局部和长期的治疗效果。受蜜蜂追踪花朵的气味来采集花蜜的现象的启发，我们通过结合微流控方法和光聚合工艺，开发了具有活性氧（ROS）响应能力的软骨靶向水凝胶微球，将软骨靶向肽和 ROS 响应纳米颗粒整合到水凝胶基质中。具有软骨靶向特性的水凝胶微球促进了更好地保留在关节腔内，并增强了纳米颗粒的细胞摄取。此外，ROS 响应纳米颗粒可以与骨关节炎（OA）诱导的细胞内 ROS 反应，导致纳米颗粒的解聚，不仅可以消除过量的 ROS 和减轻炎症，还可以促进地塞米松（Dex）和卡托醌（KGN）的释放，实现有效的 OA 治疗。结果表明，该水凝胶微球表现出良好的 ROS 响应能力，并增强了软骨形成分化以及下调促炎因子。此外，水凝胶微球类似于蜜蜂，可以靶向并有效地修复 OA 模型中的软骨。因此，可注射水凝胶微球在修复 OA 方面具有巨大的潜力，也可能为炎症性肠病的治疗提供有效途径。
