A bio-inspired nanoparticle coating for vascular healing and immunomodulatory by cGMP-PKG and NF-kappa B signaling pathways

Abstract

Drug-eluting stents (DESs) implantation is an effective method to tackle in-stent restenosis (ISR), which has been considered as an efficient treatment for coronary atherosclerosis. Although fruitful results have been achieved in treating coronary artery diseases (CAD), concern has arisen regarding the long-term safety and efficacy of DESs, primarily due to adverse events such as delayed re-endothelialization, persistent inflammatory response, and late stent thrombosis (LST). Taking inspiration from the immunomodulatory functions of camouflage strategies, this study designed a bio-inspired nanoparticle-coated stent. Briefly, the platelet membrane-coated poly (lactic-co-glycolic acid)/Rapamycin nanoparticles (PNP) were sprayed onto stents, forming a homogenous nanoparticle coating. The bilayer of poly (lactic-co-glycolic acid) (PLGA) and platelet membrane works synergistically to promote the sustained-release effect of rapamycin. In vitro studies revealed that the PNP-coated surfaces promoted the competitive adhesion of endothelia cells while inhibiting smooth muscle cells. Subsequent in vivo studies demonstrated that these surfaces expedite re-endothelialization and elicit immunomodulatory effects by regulating the cGMP-PKG and NF-kappa B signaling pathways, influencing the biosynthesis cofactors and immune system signaling. The study successfully deviced a novel and biomimetic drug-eluting stent system, unraveling its detailed functions and molecular mechanism of action for enhanced vascular healing.