Anti-neovascular therapy using novel peptides homing to angiogenic vessels.

Abstract

Cancer chemotherapy targeted to angiogenic vessels is expected to cause indirect tumor regression through the damage of the neovasculature without the induction of drug resistance. To develop a tool for neovasculature-specific drug delivery, we isolated novel peptides homing to angiogenic vessels formed by a dorsal air sac method from a phage-displayed peptide library. Three distinct phage clones that markedly accumulated in murine tumor xenografts presented PRPGAPLAGSWPGTS-, DRWRPALPVVLFPLH- or ASSSYPLIHWRPWAR-peptide respectively. After the determination of the epitope sequences of these peptides, we modified liposomes with epitope penta-peptides. Liposome modified with APRPG-peptide showed high accumulation in murine tumor xenografts, and APRPG-modified liposome encapsulating adriamycin effectively suppressed experimental tumor growth. Finally, specific binding of APRPG-modified liposome to human umbilical endothelial cells, and that of PRP-containing peptide to angiogenic vessels in human tumors, i.e., islet cell tumor and glioblastoma, were demonstrated. The present study indicates the usefulness of APRPG-peptide as a tool for anti-neovascular therapy, a novel modality of cancer treatment.

• Authors: Naoto Oku, Tomohiro Asai, Koh Watanabe, Koichi Kuromi, Mayumi Nagatsuka, Kohta Kurohane, Hironori Kikkawa, Koichi Ogino, Michinori Tanaka, Dai Ishikawa, Hideo Tsukada, Masanobu Momose, Jun Nakayama, Takao Taki
• Journal: Oncogene (Oncogene) Vol. 21 Issue 17 Pg. 2662-9 (Apr 18 2002) ISSN: 0950-9232 [Print] England
• PMID: 11965539 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Antibiotics, Antineoplastic
• Liposomes
• Lymphokines
• Peptide Library
• Peptides
• Doxorubicin

Topics

• Amino Acid Sequence
• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Cell Division (drug effects)
• Dose-Response Relationship, Drug
• Doxorubicin (pharmacology)
• Endothelium, Vascular (drug effects)
• Humans
• Injections, Subcutaneous
• Liposomes (metabolism)
• Lymphokines (pharmacology)
• Male
• Melanoma, Experimental (blood supply, pathology)
• Mice
• Mice, Inbred BALB C
• Microscopy, Confocal
• Molecular Sequence Data
• Neovascularization, Pathologic (drug therapy, pathology)
• Peptide Library
• Peptides (therapeutic use)
• Sarcoma, Experimental (blood supply, pathology)
• Tomography, Emission-Computed