Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery
Journal
Cancer Research
Journal Volume
67
Journal Issue
22
Pages
10959-10965
Date Issued
2007
Author(s)
Abstract
Antiangiogenesis therapies for the treatment of cancers hold the promise of high efficacy and low toxicity. In vivo phage display was used to identify peptides specifically targeting tumor blood vessels. The peptide SP5-52 recognized tumor neovasculature but not normal blood vessels in severe combined immunodeficiency mice bearing human tumors. Synthetic peptide was shown to inhibit the binding of PC5-52 phage particles to the tumor mass in the competitive inhibition assay. Several selected phage clones displayed the consensus motif, proline-serine-proline, and this motif was crucial for peptide binding to the tumor neovasculature. SP5-52 peptides also bound vascular endothelial growth factor-stimulated human umbilical vein endothelial cells and blood vessels of human lung cancer surgical specimens. Furthermore, this targeting phage was shown to home to tumor tissues from eight different types of human tumor xenografts following in vivo phage display experiments. An SP5-52 peptide-linked liposome carrying doxorubicin enhanced the therapeutic efficacy of the drug, markedly decreased tumor blood vessels, and resulted in higher survival rates of human lung and oral cancer-bearing xenograft mice. The current study indicates that ligand-targeted therapy offers improved therapeutic effects over conventional anticancer drug therapy, and that the peptide SP5-52 specifically targets tumor neovasculature and is a good candidate for targeted drug delivery to solid tumors. ?2007 American Association for Cancer Research.
SDGs
Other Subjects
doxorubicin; liposome; proline; protein sp5 52; serine; synthetic peptide; unclassified drug; vasculotropin; doxorubicin; peptide; peptide library; angiogenesis; animal experiment; animal model; article; bacteriophage; blood vessel; cell homing; controlled study; drug delivery system; drug effect; drug inhibition; human; human cell; in vivo study; lung cancer; mouse; mouth cancer; nonhuman; priority journal; protein binding; protein motif; protein protein interaction; SCID mouse; survival rate; tumor xenograft; umbilical vein; animal; cancer transplantation; chemistry; cytology; disease model; drug delivery system; lung tumor; mouse mutant; mouth tumor; neovascularization (pathology); pathology; tumor cell line; vascular endothelium; Animals; Cell Line, Tumor; Disease Models, Animal; Doxorubicin; Drug Delivery Systems; Endothelium, Vascular; Humans; Lung Neoplasms; Mice; Mice, SCID; Mouth Neoplasms; Neoplasm Transplantation; Neovascularization, Pathologic; Peptide Library; Peptides
Type
journal article