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.

Evaluation of a Targeted Drug‐Eluting Intravascular Nanotherapy to Prevent Neointimal Hyperplasia in an Atherosclerotic Rat Model

“…To evaluate localization, duration of localization to the site of endothelial injury, and efficacy of our injectable therapeutic after vascular intervention, the rat carotid artery balloon injury model was used as previously described. [ 7,12,23,27–30 ] Briefly, 16‐week‐old male SD ApoE‐/‐ rats were anesthetized with 1–5.0% inhaled isoflurane, and injected with atropine (0.1 mg kg −1 ) and carprofen (0.15 mg kg −1 ) subcutaneously to decrease airway secretions and for pain control, respectively. This was followed by a tail vein injection of heparin (0.1 mg kg −1 ).…”

Collagen-Binding Nanoparticles: A Scoping Review of Methods and Outcomes

“…Fourteen studies were selected based on the inclusion criteria [17][18][19][20][21][22][23][24][25][26][27][28][29][30] (Figure 1). The initial search found 603 manuscripts, out of which 108 were duplicates and were removed.…”

Targeting Inflammation With Nanosized Drug Delivery Platforms in Cardiovascular Diseases: Immune Cell Modulation in Atherosclerosis

“…Li et al used liposomes decorated with LOX-1 antibodies, Indium ( 111 In) or Gadolinium (Gd), and DiI fluorescence markers to image atherosclerotic plaques in ApoE −/− mice. Alternatively, it has been proposed to target collagen IV, which is present on the vascular basement and exposed when vascular permeability increases (Chan et al, 2011 ; Chen et al, 2013 ; Kamaly et al, 2016 ; Meyers et al, 2017 ). Also common strategies to target macrophages are based on functionalizing nanoparticles with dextran sulfate coating or peptides mimicking low-density lipoproteins (LDL) such as apolipoprotein A1 (ApoA-1), whose receptors (Class A Scavenger Receptor 1 MSR-1, and class B Scavenge Receptor CD36) are expressed on macrophages cell membrane (Canton et al, 2013 ).…”