Polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid, and focal adhesion to sites of atherosclerosis

Sudhir P. Deosarkar, Ramiro Malgor, Jie Fu, Leonard D. Kohn, Justin Hanes, Douglas J. Goetz

Research output: Contribution to journalArticle

Abstract

The increased expression of VCAM-1 on endothelial segments within plaque regions could be used as a target to deliver polymeric drug carriers selectively to sites of atherosclerosis. We probed me hypothesis that polymeric particles conjugated with a ligand for VCAM-1 exhibit selective and avid adhesion to sites of atherosclerosis. Particles made from polystyrene or the biodegradable polymer poly(sebacic acid)-block-polyerthylene glycol (PSA-PEG) were conjugated with an antibody to VCAM-1 (α-VCAM-1) or IgG (negative control). The particles were injected into the jugular vein of ApoE-/- (a murine model of atherosclerosis) or wild type mice and their adhesion to the aorta determined. α-VCAM-1 particles exhibited sig-nificantiy greater adhesion to ApoE-/- mouse aorta [32 ± 5 (mean ± SEM) particles/mm2 for polystyrene particles and 31 ±7 particles/mm2 for PSA-PEG particles] compared to the level of adhesion to wild type mouse aorta (18 ± 1 particles/mm2 for polystyrene particles and 6± 1 particles/mm2 for PSA-PEG particles). Within ApoE-/- mice, the α-VCAM-1 particles exhibited significantly greater adhesion to the aorta (32 ± 5 particles/mm2 for polystyrene particles and 31 ±7 particles/mm2 for PSA-PEG particles) compared to the adhesion of IgG particles (1 ± 1 particles/ mm2 for polystyrene particles and 2 ± 1 particles/mm2 for PSA-PEG particles). Detailed analysis of the adhesion revealed that α-VCAM-1 particles exhibited focal adhesion to plaque regions, in particular the periphery of the plaques, within the ApoE-/- mouse aorta. Combined the data demonstrate that polymeric particles conjugated with a ligand to VCAM-1 exhibit selective, avid and focal adhesion to sites of atherosclerosis providing strong evidence that VCAM-1 ligand bearing polymeric particles could be used for targeting drues selectively to atherosclerotic tissue.

Original languageEnglish (US)
Pages (from-to)400-407
Number of pages8
JournalBiotechnology and bioengineering
Volume101
Issue number2
DOIs
StatePublished - Oct 1 2008

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Keywords

  • Adhesion
  • Atherosclerosis
  • Drug delivery
  • VCAM-1

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology

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