Spatiotemporal controlled delivery of nanoparticles to injured vasculature

Juliana M. Chan, Liangfang Zhang, Rong Tong, Debuyati Ghosh, Weiwei Gao, Grace Liao, Kai P. Yuet, David Gray, June Wha Rhee, Jianjun Cheng, Gershon Golomb, Peter Libby, Robert Langer, Omid C. Farokhzad

Research output: Contribution to journalArticlepeer-review


There are a number of challenges associated with designing nanoparticles for medical applications. We define two challenges here: (i) conventional targeting against up-regulated cell surface antigens is limited by heterogeneity in expression, and (ii) previous studies suggest that the optimal size of nanoparticles designed for systemic delivery is approximately 50-150 nm, yet this size range confers a high surface area-to-volume ratio, which results in fast diffusive drug release. Here, we achieve spatial control by biopanning a phage library to discover materials that target abundant vascular antigens exposed in disease. Next, we achieve temporal control by designing 60-nm hybrid nanoparticles with a lipid shell interface surrounding a polymer core, which is loaded with slow-eluting conjugates of paclitaxel for controlled ester hydrolysis and drug release over approximately 12 days. The nanoparticles inhibited human aortic smooth muscle cell proliferation in vitro and showed greater in vivo vascular retention during percutaneous angioplasty over nontargeted controls. This nanoparticle technology may potentially be used toward the treatment of injured vasculature, a clinical problem of primary importance.

Original languageEnglish (US)
Pages (from-to)2213-2218
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Feb 2 2010
Externally publishedYes


  • Angioplasty
  • Collagen
  • Nanoparticle
  • Paclitaxel
  • Peptides

ASJC Scopus subject areas

  • General


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