Angiogenic vessel-targeting DDS by liposomalized oligopeptides.
Liposomal oligopeptides are one of the promising nanocarriers to deliver a drug, DNA or siRNA to target tissues. In this chapter, we describe our methodology to develop liposomal oligopeptides targeting to tumor angiogenic vessels. At first, we introduce our strategies to identify objective peptides. We performed in vivo biopanning using a phage-displayed peptide library and identified Ala-Pro-Arg-Pro-Gly (APRPG) peptide as a ligand for angiogenic vessels. To modify APRPG peptide on the surface of PEGylated liposomes, we synthesized a novel lipid derivative of the peptide, distearoylphosphatidylethanolamine-polyethyleneglycol-APRPG (DSPE-PEG-APRPG). The lipid derivative of APRPG peptide is expected to be readily incorporated into liposomal membrane and enables to present the peptides on the surface of PEGylated liposomes. We next describe how to evaluate the advantages of liposomal oligopeptides using specific examples; (1) Intratumoral distribution of APRPG-PEG-modified liposomes, (2) Therapeutic efficacy of adriamycin encapsulated in APRPG-PEG-modified liposomes, (3) Preparation of 5'-O-dipalmitoylphosphatidyl 2'-C-cyano-2'-deoxy-1-beta-D-arabino-pentofuranosylcytosine (DPP-CNDAC) liposomes modified with APRPG-PEG, and (4) Therapeutic experiment with APRPG-PEG-modified liposomal DPP-CNDAC.
Asai
Tomohiro
T
Department of Medical Biochemistry and Global COE, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Oku
Naoto
N
D000595:Amino Acid Sequence; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D009842:Oligopeptides / Q000737:chemistry* / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D011092:Polyethylene Glycols / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D008055:Lipids; D008081:Liposomes; D009842:Oligopeptides; C490869:alanyl-prolyl-arginyl-prolyl-glycine; D011092:Polyethylene Glycols; D004317:Doxorubicin