PAR2-targeted XCT790-loaded magnetic nanoparticles significantly inhibited osteogenic differentiation of valvular interstitial cells and alleviated aortic valve calcification and stenosis in a mouse model.
Does a PAR2-targeting magnetic nanocarrier delivering XCT790 alleviate aortic valve calcification in a murine model?
A dual-active targeting magnetic nanocarrier system delivering XCT790 successfully alleviated aortic valve calcification and stenosis in a preclinical mouse model.
Abstract Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790—an anti-calcification drug—to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient ( Ldlr −/− ) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.
Chen et al. (Tue,) conducted a other in Calcific aortic valve disease. PAR2-targeting magnetic nano-cargoes loaded with XCT790 (SR@PFeXCT) vs. PBS, XCT790 alone, or non-targeted nanoparticles was evaluated on Aortic valve calcification and stenosis (peak transvalvular jet velocity, pressure gradient, calcium deposition). PAR2-targeted XCT790-loaded magnetic nanoparticles significantly inhibited osteogenic differentiation of valvular interstitial cells and alleviated aortic valve calcification and stenosis in a mouse model.