Journal
BIOMATERIALS
Volume 35, Issue 30, Pages 8678-8686Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.06.054
Keywords
Peptide amphiphile; Atherosclerosis; VCAM-1; Self-assembly; Micelle
Funding
- DoD
- AFOSR
- National Defense Science and Engineering [32 CFR 168a]
- American Heart Association
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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. (C) 2014 Elsevier Ltd. All rights reserved.
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