Peptide-mediated targeting to tumor blood vessels of lung cancer for drug delivery.
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.
Lee
Tong-Young
TY
Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Lin
Chin-Tarng
CT
Kuo
Szu-Yao
SY
Chang
De-Kuan
DK
Wu
Han-Chung
HC
D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000188:drug therapy; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D019151:Peptide Library; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry*
D019151:Peptide Library; D010455:Peptides; D004317:Doxorubicin