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.
Bibliographical noteFunding Information:
Funding Information The US Army Research Office, the US Army Medical Research and Material Command, and Northwestern University provided funding to develop this facility. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. Sources of funding were the National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (NHLBI) T32 Training Grant (T32HL094293), the NIH/NHLBI BRP grant (5R01HL116577), the NIH National Center for Advancing Translational Sciences grant (UL1TR001422) and the American Medical Association Foundation 2015 Seed Grant. This work was also supported by Simpson Querrey Institute. The authors express their gratitude to the Northwestern University Simpson Querrey Institute for BioNanotechnology and to Lynnette Dangerfield for her administrative support. Peptide synthesis was performed in the Peptide Synthesis Core Facility of the Simpson Querrey Institute at Northwestern University. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
- neointimal hyperplasia
- vascular biology
- vascular disease