title: 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.affiliation: Department of Medical Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan. oku@u-shizuoka-ken.ac.jp
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Koh
authors.initials: K
authors.lastname: Watanabe
authors.forename: Koichi
authors.initials: K
authors.lastname: Kuromi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nagatsuka
authors.forename: Kohta
authors.initials: K
authors.lastname: Kurohane
authors.forename: Hironori
authors.initials: H
authors.lastname: Kikkawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ogino
authors.forename: Michinori
authors.initials: M
authors.lastname: Tanaka
authors.forename: Dai
authors.initials: D
authors.lastname: Ishikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.forename: Masanobu
authors.initials: M
authors.lastname: Momose
authors.forename: Jun
authors.initials: J
authors.lastname: Nakayama
authors.forename: Takao
authors.initials: T
authors.lastname: Taki
mesh_terms: D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D007279:Injections, Subcutaneous; D008081:Liposomes / Q000378:metabolism; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology; D019151:Peptide Library; D010455:Peptides / Q000627:therapeutic use*; D012513:Sarcoma, Experimental / Q000098:blood supply* / Q000473:pathology; D014055:Tomography, Emission-Computed
chemical_list: D020533:Angiogenesis Inhibitors; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D008222:Lymphokines; D019151:Peptide Library; D010455:Peptides; D004317:Doxorubicin