Development of fractalkine-targeted nanofibers that localize to sites of arterial injury

Hussein A. Kassam, David C. Gillis, Brooke R. Dandurand, Mark R. Karver, Nick D. Tsihlis, Samuel I. Stupp, Melina R. Kibbe

Research output: Contribution to journalArticle

Abstract

Atherosclerosis is the leading cause of death and disability around the world, with current treatments limited by neointimal hyperplasia. Our goal was to synthesize, characterize, and evaluate an injectable, targeted nanomaterial that will specifically bind to the site of arterial injury. Our target protein is fractalkine, a chemokine involved in both neointimal hyperplasia and atherosclerosis. We showed increased fractalkine staining in rat carotid arteries 24 h following arterial injury and in the aorta of low-density lipoprotein receptor knockout (LDLR-/-) mice fed a high-fat diet for 16 weeks. Three peptide amphiphiles (PAs) were synthesized: fractalkine-targeted, scrambled, and a backbone PA. PAs were ≥90% pure on liquid chromatography/mass spectrometry (LCMS) and showed nanofiber formation on transmission electron microscopy (TEM). Rats systemically injected with fractalkine-targeted nanofibers 24 h after carotid artery balloon injury exhibited a 4.2-fold increase in fluorescence in the injured artery compared to the scrambled nanofiber (p < 0.001). No localization was observed in the non-injured artery or with the backbone nanofiber. Fluorescence of the fractalkine-targeted nanofiber increased in a dose dependent manner and was observed for up to 48 h. These data demonstrate the presence of fractalkine after arterial injury and the localization of our fractalkine-targeted nanofiber to the site of injury and serve as the foundation to develop this technology further.

Original languageEnglish
Article number420
JournalNanomaterials
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 2020

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Keywords

  • Arterial injury
  • Cardiovascular disease prevention
  • Fractalkine
  • Nanofibers
  • Neointimal hyperplasia
  • Targeted delivery vehicle
  • Targeted therapeutic

ASJC Scopus subject areas

  • Chemical Engineering(all)
  • Materials Science(all)

Cite this

Kassam, H. A., Gillis, D. C., Dandurand, B. R., Karver, M. R., Tsihlis, N. D., Stupp, S. I., & Kibbe, M. R. (2020). Development of fractalkine-targeted nanofibers that localize to sites of arterial injury. Nanomaterials, 10(3), [420]. https://doi.org/10.3390/nano10030420