Se-HA wrapped core-shell codelivery nanoparticles with ROS-response for targeted enhance chondrogenesis

Chondrodysplasia presents with abnormal chondrocyte differentiation and altered cartilage extracellular matrix, which restricts cartilage and bone growth. Kartogenin (KGN) is recognized as a chondroinductive molecule, whereas the limitation of hydrophobicity and low bioavailability are obstacles to therapy. Nanocarriers for drug delivery can potentially defeat some of the challenges of drug delivery of hydrophobic species. Herein, ROS-responsive core-shell codelivery nanocarriers were developed for chondrogenesis with a core consisting of mesoporous silica nanoparticles (MSN) loaded with KGN and embedded with ultrasmall Prussian blue (USPB), and a shell consisting of selenized hyaluronic acid (Se-HA). MKP@Se-HA nanoparticles effectively improved the bioavailability of KGN. The embedded USPB enhanced structural stability and antioxidant properties, while Se-HA coating targeted chondrocytes via CD44 and employed diselenide bonds as ROS-responsive to achieve KGN release at lesion sites. In vitro and in vivo experiments demonstrated that MKP@Se-HA nanoparticles could promote chondrocyte proliferation and differentiation by upregulating SOX9 and Col II expression. Meanwhile, MKP@Se-HA nanoparticles had a positive effect in the zebrafish chondrodysplasia model by modulating the formation of cartilage matrix and reducing apoptotic cells. Overall, the prepared core-shell codelivery nanoparticles offer a promising strategy for improving chondrodysplasia by synergistically promoting chondrocyte proliferation and differentiation.