Micelles derivatized with octreotide as potential target‐selective contrast agents in MRI

Abstract

New amphiphilic monomers (OCA-DTPAGlu and OCA-DOTA) containing, in the same molecule, three different functions: (i) the chelating agent (DTPAGlu or DOTA) able to coordinate gadolinium ion, (ii) the octreotide bioactive peptide able to target somatostatin receptors, and (iii) a hydrophobic moiety with two 18-carbon atoms alkyl chains have been designed and synthesized by solid-phase methods. The novel amphiphilic monomers aggregate, in water solution, giving stable micelles at very low concentration (cmc values of 2.3 x 10(-6) mol kg(-1) and 2.5 x 10(-6) mol kg(-1) for OCA-DTPAGlu and OCA-DOTA, respectively) as confirmed by fluorescence spectroscopy. Fluorescence studies and circular dichroism experiments indicate, for the two compounds as well as for their gadolinium complexes (OCA-DOTA(Gd) and OCA-DTPAGlu(Gd)), the complete exposure of octreotide on the micelle surface, and the predominant presence of an antiparallel beta-sheet peptide conformation characterized by a beta-like turn. The high relaxivity value (r(1p) = 13.9 mM(-1) s(-1) at 20 MHz and 25 degrees C), measured for micelles obtained by the gadolinium complex OCA-DTPAGlu(Gd), indicates these aggregates as promising target-selective magnetic resonance imaging (MRI) contrast agents.

Peptide‐labeled supramolecular aggregates as selective doxorubicin carriers for delivery to tumor cells

“…19 Finally, the gadolinium complexes of this new class of supramolecular aggregates have been proposed as high relaxivity and target selective contrast agents in MRI. 15,17 In this article, we report on new liposomal aggregates obtained by combining together, in a 90:10 molar ratio, the two monomers schematized in Figure 1. Monomer (a), (C18) 2 DOTA, contains two hydrocarbon chains in the hydrophobic region and the anionic DOTA chelating agent as hydrophilic moiety.…”

Self-assembled peptide nanomaterials for biomedical applications: promises and pitfalls

“…107,108 Bull et al synthesized two Gd(III) conjugated amphiphilic peptides (DOTA-KK(K)K-LL-CCC-K-C 16 and DOTA-KGRGDS(K)K-LLL-AAA-K-C 16 ) to form spherical and tubular structures. Since the self-assembling structure could increase the molecular weight of Gd, the rotational correlation time and consequently the relaxivity were enhanced.…”

Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs

“…13 In the last few years, many different aggregates have been developed to carry chemotherapeutic drugs to SSTR2 expressing tumors by coupling to the OCT peptide. 61 Octreotide labeled aggregates may be obtained following the two approaches presented above. One strategy was based on synthesizing the OCT on trityl resin in solid phase and coupling the other molecular building blocks step by step.…”

“…In order to characterize these aggregates for their suitability for in vivo use as selective targeting tools, it is possible to study peptide properties on the aggregate surface through classical chemical physical methods. Morisco et al 61 developed OCT containing aggregates for use as drug carriers and magnetic resonance imaging (MRI) contrast agents. The monomers, synthesized on solid phase, contain, in the same molecule, three different functions: the chelating agent (DTPAGlu or DOTA); OCT; and a hydrophobic moiety based on two C18 hydrophobic chains.…”