title: Peptide-containing aggregates as selective nanocarriers for therapeutics.
abstract: New nanocarriers are obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-111 complexes linked to the same hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of approximately 40 A and length >700 A, open bilayer fragments with thickness approximately 65 A, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin.
authors.affiliation: CIRPeB, Department of Biological Sciences & IBB CNR, University of Naples Federico II, Via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloj
authors.forename: Laura
authors.initials: L
authors.lastname: Tarallo
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Gaetano
authors.initials: G
authors.lastname: Mangiapia
authors.forename: Mauro
authors.initials: M
authors.lastname: Vaccaro
authors.forename: Carlo
authors.initials: C
authors.lastname: Pedone
authors.forename: Luigi
authors.initials: L
authors.lastname: Paduano
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
mesh_terms: D000818:Animals; D002766:Cholecystokinin / Q000737:chemistry* / Q000493:pharmacokinetics; D020285:Cryoelectron Microscopy; D004337:Drug Carriers / Q000737:chemistry*; D005260:Female; D007205:Indium Radioisotopes; D051379:Mice; D008823:Micelles; D049329:Nanostructures / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry* / Q000493:pharmacokinetics; D012542:Scattering, Radiation; D014018:Tissue Distribution
chemical_list: D004337:Drug Carriers; D007205:Indium Radioisotopes; D008823:Micelles; D010446:Peptide Fragments; C410885:cholecystokinin 8; D002766:Cholecystokinin