TY  - JOUR
AU  - Accardo, A.
AU  - Mansi, R.
AU  - Mirisco, A.
AU  - Mangiapia, G.
AU  - Paduano, L.
AU  - Tesauro, D.
AU  - Radulescu, A.
AU  - Aurilio, M.
AU  - Aloj, L.
AU  - Arra, C.
AU  - Morelli, G.
TI  - Peptide modified nanocarriers for selective targeting of bombesin receptors
JO  - Molecular BioSystems
VL  - 6
SN  - 1742-206X
CY  - Cambridge
PB  - Royal Society of Chemistry
M1  - PreJuSER-9565
SP  - 878 - 887
PY  - 2010
N1  - We thank Prof. Helmut Maecke, University Hospital Basel, Switzerland for the helpful discussions and suggestions. We are indebted to EMIL, European Molecular Imaging Laboratories, for financial support. Some of us (LP, GM, AR) wish to thank the Forschungszentrum Julich for provision of beam time.
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)(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).
KW  - Cell Line, Tumor
KW  - Chelating Agents: chemistry
KW  - Heterocyclic Compounds, 1-Ring: chemistry
KW  - Humans
KW  - Liposomes: chemistry
KW  - Models, Theoretical
KW  - Molecular Structure
KW  - Peptides: chemistry
KW  - Peptides: metabolism
KW  - Receptors, Bombesin: metabolism
KW  - Chelating Agents (NLM Chemicals)
KW  - Heterocyclic Compounds, 1-Ring (NLM Chemicals)
KW  - Liposomes (NLM Chemicals)
KW  - Peptides (NLM Chemicals)
KW  - Receptors, Bombesin (NLM Chemicals)
KW  - 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20567774
UR  - <Go to ISI:>//WOS:000277315800015
DO  - DOI:10.1039/b923147a
UR  - https://juser.fz-juelich.de/record/9565
ER  -