Nanoparticle targeting to diseased vasculature for imaging and therapy

Abstract

Significant challenges remain in targeting drugs to diseased vasculature; most important being rapid blood flow with high shear, limited availability of stable targets, and heterogeneity and recycling of cellular markers. We developed nanoparticles (NPs) to target degraded elastic lamina, a consistent pathological feature in vascular diseases. In-vitro organ and cell culture experiments demonstrated that these NPs were not taken up by cells, but instead retained within the extracellular space; NP binding was proportional to the extent of elastic lamina damage. With three well-established rodent models of vascular diseases such as aortic aneurysm (calcium chloride mediated aortic injury in rats), atherosclerosis (fat-fed apoE-/- mice), and vascular calcification (warfarin + vitamin K injections in rats), we show precise NPs spatial targeting to degraded vascular elastic lamina while sparing healthy vasculature when NPs were delivered systemically. Nanoparticle targeting degraded elastic lamina is attractive to deliver therapeutic or imaging agents to the diseased vasculature.

From the clinical editor: This novel work focuses on nanoparticle targeting of degraded elastic lamina in a variety of diseases, including atherosclerosis, vascular calcification, and aneurysm formation, and demonstrates the feasibility to deliver therapeutic or imaging agents to the diseased vasculature.

Keywords: Elastin; Extracellular matrix targeting; Nanoparticles; Vascular nanomedicine.