TY - JOUR
T1 - Peptide modified nanocarriers for selective targeting of bombesin receptors
AU - Accardo, Antonella
AU - Mansi, Rosalba
AU - Morisco, Anna
AU - Mangiapia, Gaetano
AU - Paduano, Luigi
AU - Tesauro, Diego
AU - Radulescu, Aurel
AU - Aurilio, Michela
AU - Aloj, Luigi
AU - Arra, Claudio
AU - Morelli, Giancarlo
PY - 2010
Y1 - 2010
N2 - 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)2DOTA, capable of forming stable complexes with the radioactive 111In(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)2L5-peptide, or a longer spacer consisting of a Peg3000 residue in (C18)2Peg3000-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 Rh around 200 nm and bilayer thickness, d, of 4 nm. In vitro data show specific binding of the 111In-(C18)2DOTA/(C18)2L5-[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 111In-(C18) 2DOTA/(C18)2L5-[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).
AB - 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)2DOTA, capable of forming stable complexes with the radioactive 111In(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)2L5-peptide, or a longer spacer consisting of a Peg3000 residue in (C18)2Peg3000-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 Rh around 200 nm and bilayer thickness, d, of 4 nm. In vitro data show specific binding of the 111In-(C18)2DOTA/(C18)2L5-[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 111In-(C18) 2DOTA/(C18)2L5-[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).
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U2 - 10.1039/b923147a
DO - 10.1039/b923147a
M3 - Article
C2 - 20567774
AN - SCOPUS:77952354303
VL - 6
SP - 878
EP - 887
JO - Molecular BioSystems
JF - Molecular BioSystems
SN - 1742-206X
IS - 5
ER -