title: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sinha
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Aleksey
authors.initials: A
authors.lastname: Shaporev
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Nasim
authors.initials: N
authors.lastname: Nosoudi
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Alexey
authors.initials: A
authors.lastname: Vertegel
authors.affiliation: Cell Biology & Anatomy, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Lessner
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA. Electronic address: narenv@clemson.edu.
authors.forename: Naren
authors.initials: N
authors.lastname: Vyavahare
mesh_terms: D000818:Animals; D001014:Aortic Aneurysm / Q000175:diagnosis; D050197:Atherosclerosis / Q000175:diagnosis; D003952:Diagnostic Imaging / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D061205:Vascular Calcification / Q000175:diagnosis
chemical_list: D011108:Polymers; D019344:Lactic Acid
keywords: Elastin; Extracellular matrix targeting; Nanoparticles; Vascular nanomedicine