pH-responsive and hyaluronic acid-functionalized metal–organic frameworks for therapy of osteoarthritis
Feng Xiong, Zainen Qin, Haimin Chen, Qiumei Lan, Zetao Wang, Nihan Lan, Yuan Yang, Li Zheng, Jinmin Zhao, Dan Kai
Abstract
Drug therapy of osteoarthritis (OA) is limited by the short retention and lacking of stimulus-responsiveness after intra-articular (IA) injection. The weak acid microenvironment in joint provides a potential trigger for controlled drug release systems in the treatment of OA. Herein, we developed an pH-responsive metal - organic frameworks (MOFs) system modified by hyaluronic acid (HA) and loaded with an anti-inflammatory protocatechuic acid (PCA), designated as MOF@HA@PCA, for the therapy of OA. Results demonstrated that MOF@HA@PCA could smartly respond to acidic conditions in OA microenvironment and gradually release PCA, which could remarkably reduce synovial inflammation in both IL-1β induced chondrocytes and the OA joints. MOF@HA@PCA also down-regulated the expression of inflammatory markers of OA and promoted the expression of cartilage-specific makers. This work may provide a new insight for the design of efficient nanoprobes for precision theranostics of OA .