Active targeting of early and mid-stage atherosclerotic plaques using self-assembled peptide amphiphile micelles

Laurie B. Mlinar, Eun Ji Chung, Emily A. Wonder, Matthew Tirrell

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Inflammatory cell adhesion molecules expressed by endothelial cells on the luminal surface of atherosclerotic plaques, such as vascular cell adhesion molecule-1 (VCAM-1), provide a rational target for diagnostic and therapeutic delivery vehicles. Therefore, the potential of using spherical, self-assembled micelles synthesized from VCAM-1 targeted peptide amphiphile molecules was examined for the ability to specifically bind to both early and mid-stage atherosclerotic plaques. In vitro, cells incubated with VCAM-1 targeted and dye-labeled micelles show enhanced fluorescence signal as compared to cells incubated with a PEG micelle control. In vivo, VCAM-1 targeted and Cy7-labeled peptide amphiphile micelles were shown to specifically accumulate at atherosclerotic plaques in both early and mid-stage ApoE -/- mice through co-localization of Cy7 signal with anti-VCAM-1 antibody staining in fixed tissue. No specific accumulation was observed with a PEG micelle control. Histological analysis of excised tissue provided evidence for the in vivo biocompatibility of these micelle formulations as no tissue damage was observed. These results demonstrate that VCAM-1 targeted micelles have potential as a platform for targeted drug delivery to multiple stages of atherosclerotic plaque formation due to their established specificity and safety.

Original languageEnglish (US)
Pages (from-to)8678-8686
Number of pages9
JournalBiomaterials
Volume35
Issue number30
DOIs
StatePublished - Oct 2014
Externally publishedYes

Keywords

  • Atherosclerosis
  • Micelle
  • Peptide amphiphile
  • Self-assembly
  • VCAM-1

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