Multi-ligand poly(l-lactic-co-glycolic acid) nanoparticles inhibit activation of endothelial cells

Hao Xu, Soujanya Kona, Lee Chun Su, Yi Ting Tsai, Jing Fei Dong, Emmanouil S Brilakis, Liping Tang, Subhash Banerjee, Kytai T. Nguyen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Endothelial cell (EC) activation and inflammation is a key step in the initiation and progression of many cardiovascular diseases. Targeted delivery of therapeutic reagents to inflamed EC using nanoparticles is challenging as nanoparticles do not arrest on EC efficiently under high shear stress. In this study, we developed a novel polymeric platelet-mimicking nanoparticle for strong particle adhesion onto ECs and enhanced particle internalization by ECs. This nanoparticle was encapsulated with dexamethasone as the anti-inflammatory drug, and conjugated with polyethylene glycol, glycoprotein 1b, and trans-activating transcriptional peptide. The multi-ligand nanoparticle showed significantly greater adhesion on P-selectin, von Willebrand Factor, than the unmodified particles, and activated EC in vitro under both static and flow conditions. Treatment of injured rat carotid arteries with these multi-ligand nanoparticles suppressed neointimal stenosis more than unconjugated nanoparticles did. These results indicate that this novel multi-ligand nanoparticle is efficient to target inflamed EC and inhibit inflammation and subsequent stenosis.

Original languageEnglish (US)
Pages (from-to)570-578
Number of pages9
JournalJournal of cardiovascular translational research
Volume6
Issue number4
DOIs
StatePublished - Aug 1 2013

Keywords

  • Endothelial cell
  • Glycoprotein 1b
  • Nanoparticle
  • Trans-activating transcriptional peptide

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

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