Abstract

Synovial inflammation and cartilage degeneration are two crucial pathologic features in temporomandibular joint osteoarthritis (TMJ OA). Cartilage repair can be very thorny in inflammatory environment, which is highly associated with the activated macrophages. Thus, simultaneous inflammation suppression and cartilage repair are strongly required. However, the clinically used intra-articular injection agents face the problems of insufficient inflammation suppression, deficient cartilage repair and non-targeted therapy. Hence, we developed the novel dual-targeted lipid nanoparticles (LNPs) loaded with miR-330-3p, an important inflammation inhibitor, and kartogenin (KGN), a pro-chondrogenic small molecular, for synergistic anti-inflammation and cartilage repair of TMJ OA. The folic acid (FA) and collagen II-targeting peptide (WYRGRL) were modified on the surface of LNPs for precise delivery to macrophages or chondrocytes, respectively. The dual-targeted miR-330-3p@FA-LNP and KGN@WYRGRL-LNP (KGN@W-LNP) both manifested high bioavailability and selectively active cellular uptake. Furthermore, it functioned synergistically to alleviate synovium inflammation and cartilage degeneration via modulating the M1 to M2 repolarization of macrophages and maintaining the homeostasis of chondrocytes, with a low intra-articular injection dose of miR-330-3p@FA-LNP (0.0125 nmol) and KGN@W-LNP (0.025 nmol) in vivo. RNA-seq and further validation demonstrated that miR-330-3p functioned by inhibiting SPARC and KGN functioned by upregulating EPHB4. In summary, this dual-targeted LNPs system provides a promising therapeutic strategy for TMJ OA treatment.

Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call