title: Liposomal doxorubicin doubly functionalized with CCK8 and R8 peptide sequences for selective intracellular drug delivery.
abstract: A new dual-ligand liposomal doxorubicin delivery system, which couples targeting to enhanced cellular uptake and may lead to a more efficient drug delivery system, is here designed and synthetized. Liposomes based on the composition 1,2-dioleoyl-sn-glycero-3-phosphocholine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-Peg2000-R8/(C18)2-L5-SS-CCK8 (87/8/5 mol/mol/mol) were prepared and loaded with doxorubicin. Presence of the two peptides on the external surface is demonstrated by fluorescence resonance energy transfer assay. The combination of the R8 cell-penetrating peptide and of the CCK8 targeting peptide (homing peptide) on the liposome surface is obtained by combining pre-modification and post-modification methods. In the dual-ligand system, the CCK8 peptide is anchored to the liposome surface by using a disulfide bond. This chemical function is inserted in order to promote the selective cleavage of the homing peptide under the reductive conditions expected in proximity of the tumor site, thus allowing targeting and internalization of the liposomal drug.
authors.affiliation: Department of Pharmacy and CIRPeB, Centro Interuniversitario di Ricerca sui Peptidi Bioattivi - University of Naples 'Federico II', Via Mezzocannone 16, 80134, Naples, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Ringhieri
authors.forename: Carlo
authors.initials: C
authors.lastname: Diaferia
authors.forename: Stefania
authors.initials: S
authors.lastname: Galdiero
authors.forename: Rosanna
authors.initials: R
authors.lastname: Palumbo
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
mesh_terms: D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D009842:Oligopeptides; D010455:Peptides; C506643:liposomal doxorubicin; C500307:octa-arginine peptide; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: cell-penetrating peptides; click chemistry; drug delivery systems; homing peptides; liposomes