title: Systemically administered collagen-targeted gold nanoparticles bind to arterial injury following vascular interventions.
abstract: Surgical and endovascular therapies for severe atherosclerosis often fail due to the development of neointimal hyperplasia and arterial restenosis. Our objective was to synthesize, characterize, and evaluate the targeting specificity and biocompatibility of a novel systemically injected nanoparticle. We hypothesize that surface-functionalization of gold nanoparticles (AuNPs) with a collagen-targeting peptide will be biocompatible and target specifically to vascular injury. 13 nm AuNPs were surface functionalized with a peptide-molecular fluorophore and targeted to collagen (T-AuNP) or a scrambled peptide sequence (S-AuNP). After rat carotid artery balloon injury and systemic injection of T-AuNP or S-AuNP, arteries and organs were harvested and assessed for binding specificity and biocompatibility. The T-AuNP bound with specificity to vascular injury for a minimum of 24 h. No significant inflammation was evident locally at arterial injury or systemically in major organs. The T-AuNP did not impact endothelial cell viability or induce apoptosis at the site of injury in vivo. No major changes were evident in hepatic or renal blood chemistry profiles. Herein, we synthesized a biocompatible nanoparticle that targets to vascular injury following systemic administration. These studies demonstrate proof-of-principle and serve as the foundation for further T-AuNP optimization to realize systemic, targeted delivery of therapeutics to the sites of vascular injury.
authors.affiliation: Department of Surgery, Northwestern University, Chicago, Illinois.|Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.
authors.forename: Molly Wasserman
authors.initials: MW
authors.lastname: Meyers
authors.affiliation: Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.|Department of Urology, Northwestern University, Chicago, Illinois.
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Rink
authors.affiliation: Department of Surgery, Northwestern University, Chicago, Illinois.|Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.
authors.forename: Qun
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Surgery, Northwestern University, Chicago, Illinois.|Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Kelly
authors.affiliation: Department of Surgery, Northwestern University, Chicago, Illinois.|Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.
authors.forename: Janet M
authors.initials: JM
authors.lastname: Vercammen
authors.affiliation: Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.|Department of Urology, Northwestern University, Chicago, Illinois.
authors.forename: Colby S
authors.initials: CS
authors.lastname: Thaxton
authors.affiliation: Department of Surgery, Northwestern University, Chicago, Illinois melina_kibbe@med.unc.edu.|Simpson Querrey Institute for BioNanotechnology, Chicago, Illinois.|Department of Surgery, University of North Carolina, Chapel Hill, North Carolina.
authors.forename: Melina R
authors.initials: MR
authors.lastname: Kibbe
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D006046:Gold; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D057772:Vascular System Injuries / Q000378:metabolism*
chemical_list: D006046:Gold; D003094:Collagen
keywords: Atherosclerosis; neointimal hyperplasia; restenosis; vascular biology; vascular disease