In vivo phage display and vascular heterogeneity: implications for targeted medicine.
The vascular endothelium expresses differential receptors depending on the functional state and tissue localization of its cells. A method to characterize this receptor heterogeneity with phage display random peptide libraries has been developed. Using this technology, several peptide ligands have been isolated that home to tissue-specific endothelial cell receptors following intravenous administration. Such peptide ligands, or antibodies directed against specific vascular receptors, can be used to target therapeutic compounds or imaging agents to endothelial cells in vitro and in vivo. Recent advances in the field include identification of novel endothelial receptors expressed differentially in normal and pathological conditions and the isolation of peptides or antibody ligands to such receptors in in vitro assays, in animal models and in a human patient. These milestones, which extend the 'functional map' of the vasculature, should lead to clinical applications in diseases such as cancer and other conditions that exhibit distinct vascular characteristics.
Trepel
Martin
M
University of Freiburg Medical Center, Department of Hematology and Oncology and Institute for Molecular Medicine and Cell Research, Hugstetter Strasse 55, D-79106, Freiburg, Germany.
Arap
Wadih
W
Pasqualini
Renata
R
D004730:Endothelium, Vascular / Q000378:metabolism*; D015316:Genetic Therapy; D006801:Humans; D008024:Ligands; D018919:Neovascularization, Physiologic; D019151:Peptide Library; D011956:Receptors, Cell Surface / Q000378:metabolism
D008024:Ligands; D019151:Peptide Library; D011956:Receptors, Cell Surface