title: Peptide modified nanocarriers for selective targeting of bombesin receptors.
abstract: The present work describes new supramolecular aggregates obtained by co-assembling two different amphiphilic molecules, one containing the bioactive bombesin peptide (BN), or a scramble sequence, and the other, the DOTA chelating agent, (C18)(2)DOTA, capable of forming stable complexes with the radioactive (111)In(III) isotope. The peptide in the amphiphilic monomer is spaced by the lipophilic moiety through ethoxylic spacers of different length: a shorter spacer with five units of dioxoethylene moieties in (C18)(2)L5-peptide, or a longer spacer consisting of a Peg3000 residue in (C18)(2)Peg3000-peptide. Structural characterization by SANS and DLS techniques indicates that, independently from the presence of the peptide containing monomer in the final composition, the predominant aggregates are liposomes of similar shape and size with a hydrodynamic radius R(h) around 200 nm and bilayer thickness, d, of 4 nm. In vitro data show specific binding of the (111)In-(C18)(2)DOTA/(C18)(2)L5-[7-14]BN 90:10 liposomes in receptor expressing cells. However, the presence of the Peg3000 unit on the external liposomal surface, could hide the peptide and prevent the receptor binding. In vivo experiments using (111)In-(C18)(2)DOTA/(C18)(2)L5-[7-14]BN show the expected biological behavior of aggregates of such size and molecular composition, moreover there is an increase in concentration of the GRPR targeting aggregate in the tumors compared to control at the 48 h time point evaluated (2.4% ID/g versus 1.6% ID/g).
authors.affiliation: Department of Biological Sciences, CIRPeB, University of Naples Federico II, & IBB-CNR, Via Mezzocannone 16, 80134 Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Accardo
authors.forename: Rosalba
authors.initials: R
authors.lastname: Mansi
authors.forename: Anna
authors.initials: A
authors.lastname: Morisco
authors.forename: Gaetano
authors.initials: G
authors.lastname: Mangiapia
authors.forename: Luigi
authors.initials: L
authors.lastname: Paduano
authors.forename: Diego
authors.initials: D
authors.lastname: Tesauro
authors.forename: Aurel
authors.initials: A
authors.lastname: Radulescu
authors.forename: Michela
authors.initials: M
authors.lastname: Aurilio
authors.forename: Luigi
authors.initials: L
authors.lastname: Aloj
authors.forename: Claudio
authors.initials: C
authors.lastname: Arra
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Morelli
mesh_terms: D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D008081:Liposomes / Q000737:chemistry; D008962:Models, Theoretical; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D018004:Receptors, Bombesin / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D008081:Liposomes; D010455:Peptides; D018004:Receptors, Bombesin; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid