title: Novel RGD lipopeptides for the targeting of liposomes to integrin-expressing endothelial and melanoma cells.
abstract: RGD peptides targeting alphav-integrins are promising ligands for the generation of vascular targeting agents. We isolated from phage display RGD motif libraries novel high-affinity cyclic RGD peptides by selection on either endothelial or melanoma cells. Although the starting sequences contained only two cysteine residues flanking the RGD motif, several of the isolated peptides possessed four cysteine residues. A high-affinity peptide (RGD10) constrained by only one disulfide bond was used to generate novel lipopeptides composed of a lipid anchor, a short flexible spacer and the peptide ligand conjugated to the spacer end. Incorporation of RGD10 lipopeptides into liposomes resulted in specific and efficient binding of the liposomes to integrin-expressing cells. In vivo experiments applying doxorubicin-loaded RGD10 liposomes in a C26 colon carcinoma mouse model demonstrated improved efficacy compared with free doxorubicin and untargeted liposomes.
authors.affiliation: Vectron Therapeutics AG, Rudolf-Breitscheid-Strasse 24, 35037 Marburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hölig
authors.forename: Miriam
authors.initials: M
authors.lastname: Bach
authors.forename: Tina
authors.initials: T
authors.lastname: Völkel
authors.forename: Thomas
authors.initials: T
authors.lastname: Nahde
authors.forename: Sven
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.forename: Roland E
authors.initials: RE
authors.lastname: Kontermann
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy; D003110:Colonic Neoplasms / Q000188:drug therapy; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology; D042783:Endothelial Cells / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D008074:Lipoproteins / Q000378:metabolism*; D008081:Liposomes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism*; D019151:Peptide Library; D010455:Peptides / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D000903:Antibiotics, Antineoplastic; D016023:Integrins; D008074:Lipoproteins; D008081:Liposomes; D009842:Oligopeptides; D019151:Peptide Library; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid; D004317:Doxorubicin