title: Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells.
abstract: Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd]) have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide) sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2) receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents.
authors.affiliation: Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Napoli.
authors.forename: Paola
authors.initials: P
authors.lastname: Ringhieri
authors.affiliation: Department of Neurological Biomedical and Movement Sciences.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mannucci
authors.affiliation: Department of Neurological Biomedical and Movement Sciences.
authors.forename: Giamaica
authors.initials: G
authors.lastname: Conti
authors.affiliation: Department of Neurological Biomedical and Movement Sciences.
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolato
authors.affiliation: Section of Immunology, Department of Medicine.
authors.forename: Giulio
authors.initials: G
authors.lastname: Fracasso
authors.affiliation: Department of Informatics, University of Verona, Verona, Italy.
authors.forename: Pasquina
authors.initials: P
authors.lastname: Marzola
authors.affiliation: Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Napoli.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
authors.affiliation: Department of Pharmacy and Interuniversity Research Centre on Bioactive Peptides (CIRPeB), University of Naples "Federico II", Napoli.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems / Q000379:methods*; D000067493:Dynamic Light Scattering; D004705:Endocytosis / Q000187:drug effects; D005260:Female; D006801:Humans; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D010455:Peptides / Q000737:chemistry* / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D060327:Solid-Phase Synthesis Techniques; D013501:Surface-Active Agents
chemical_list: D008081:Liposomes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D013501:Surface-Active Agents
keywords: KCCYSL peptide; anti-HER2 liposomes; branched peptides; breast cancer; click chemistry; target peptide