Combinatorial ligand-directed lung targeting

Ricardo J. Giordano, Julianna K. Edwards, Rubin M. Tuder, Wadih Arap, Renata Pasqualini

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Phage display of random peptide libraries is a powerful, unbiased method frequently used to discover ligands for virtually any protein of interest and to reveal functional protein-protein interaction partners. Moreover, in vivo phage display permits selection of peptides that bind specifically to different vascular beds without any previous knowledge pertaining to the nature of their corresponding receptors. Vascular targeting exploits molecular differences inherent in blood vessels within given organs and tissues, as well as diversity between normal and angiogenic blood vessels. Over the years, our group has identified phage capable of homing to lung blood vessels based on screenings using immortalized lung endothelial cells combined with in vivo selections after intravenous administration of combinatorial libraries. Peptides targeting lung vasculature have been extensively characterized and a lead homing peptide has shown interesting biological properties, bringing novel insights as to the implications of lung endothelial cell apoptosis in the pathogenesis of emphysema. We have also designed and developed targeted nanoparticles with imaging capabilities and/or drug delivery functions by combining phage display technology and elemental gold (Au) nanoparticles, constituting a promising platform for the development of therapeutic agents for imaging and treatment of lung disorders. Given the important role of the endothelium in the pathogenesisandprogression of several diseases associated with the airways, ligand-directed discovery of lung vascular markers is an important milestone toward the development of future targeted therapies.

Original languageEnglish (US)
Pages (from-to)411-415
Number of pages5
JournalProceedings of the American Thoracic Society
Volume6
Issue number5
DOIs
StatePublished - Aug 15 2009
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Pulmonary and Respiratory Medicine

Keywords

  • Lung
  • Phage display
  • Vascular targeting

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