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.
Highlights
Atherosclerosis is the leading cause of death and disability in the United States, affecting more than one in three Americans (Mozaffarian et al 2015)
We found that the T-AuNP and scrambled AuNP (S-AuNP) had no effect on rat aortic smooth muscle cells (RASMC) or rat adventitial arterial fibroblasts (RAAF) viability, death, or proliferation after 4 h and 24 h of exposure
The T-AuNP remains bound to arterial injury for a minimum of 24 h, and potentially up to 96 h, and is biocompatible in vivo, inducing no inflammatory changes, no a 2017 The Authors
Summary
Atherosclerosis is the leading cause of death and disability in the United States, affecting more than one in three Americans (Mozaffarian et al 2015). Current surgical and endovascular therapies to treat severe CAD and PAD, including balloon angioplasty and stenting, endarterectomy, and surgical bypass grafting, are costly, and often fail as a result of neointimal hyperplasia and subsequent arterial restenosis (Clowes et al 1983; Groschel et al 2005; Inoue et al 2011; Kornowski et al 1998; Welt and Rogers 2002). Drug-eluting stents, designed to provide arterial patency while preventing neointimal hyperplasia, indiscriminately inhibit cell proliferation within the stented artery, causing delayed reendothelialization and resulting in an unacceptable rate of in-stent thrombosis and death (Inoue et al 2011; Kastrati et al 2005). There exists a clear need for new technology that will enable safe revascularization and improve atherosclerotic arterial patency while minimizing patient exposure to long-term risks
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