Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications

Antonella Accardo, Anna Morisco, Eliana Gianolio, Diego Tesauro, Gaetano Mangiapia, Aurel Radulescu, Astrid Brandt, Giancarlo Morelli

Research output: Contribution to journalArticle

Abstract

New mixed nanoparticles were obtained by self-aggregation of two amphiplic monomers. The first monomer (C18)2L5-Oct contains two C18 hydrophobic moieties bound to the N-terminus of the cyclic peptide octreotide, and spaced from the bioactive peptide by five units of dioxoethylene linkers. The second monomer, (C18)2DTPAGlu, (C18)2DTPA or (C18)2DOTA, and the corresponding Gd(III) complexes, contains two C18 hydrophobic moieties bound through a lysine residue to different polyamino-polycarboxy ligands: DTPAGlu, DTPA or DOTA. Mixed aggregates have been obtained and structurally characterized by small angle neutron scattering (SANS) techniques and for their relaxometric behavior. According to a decrease of negative charges in the surfactant head-group, a total or a partial micelle-to-vesicle transition is observed by passing from (C18)2DTPAGlu to (C18)2DOTA. The thicknesses of the bilayers are substantially constant, around 50 Å, in the analyzed systems. Moreover, the mixed aggregates, in which a small amount of amphiphilic octreotide monomer (C18)2L5-Oct (10% mol/mol) was inserted, do not differ significantly from the respective self-assembled systems. Fluorescence emission of tryptophan residue at 340 nm indicates low mobility of water molecules at the peptide surface. The proton relaxivity of mixed aggregates based on (C18)2DTPAGlu(Gd), (C18)2DTPA(Gd) and (C18)2DOTA(Gd) resulted to be 17.6, 15.2 and 10.0 mM-1 s-1 (at 20 MHz and 298K), respectively. The decrease in the relaxivity values can be ascribed to the increase in τM (81, 205 and 750 ns). The presence of amphiphilic octreotide monomer exposed on mixed aggregate surface gives the entire nanoparticles a potential binding selectivity toward somatostatin sstr2 receptor subtype, and these systems could act as MRI target-specific contrast agent. Mixed nanoparticles (micelles and liposomes) are obtained by co-aggregation of lipophilic octreotide with gadolinium complex containing amphiphilic monomers for MRI applications.

Original languageEnglish
Pages (from-to)154-162
Number of pages9
JournalJournal of Peptide Science
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Octreotide
Gadolinium
Nanoparticles
Magnetic resonance imaging
Monomers
Peptides
Micelles
Small Angle Scattering
Somatostatin Receptors
Cyclic Peptides
Pentetic Acid
Neutrons
Agglomeration
Surface-Active Agents
Liposomes
Tryptophan
Contrast Media
Lysine
Protons
Fluorescence

Keywords

  • Amphiphilic gadolinium complexes
  • MRI contrast agents
  • Octreotide peptide
  • Small-angle neutron scattering
  • Supramolecular aggregates

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Medicine
  • Molecular Biology
  • Biochemistry
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

Cite this

Accardo, A., Morisco, A., Gianolio, E., Tesauro, D., Mangiapia, G., Radulescu, A., ... Morelli, G. (2011). Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications. Journal of Peptide Science, 17(2), 154-162. https://doi.org/10.1002/psc.1308

Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications. / Accardo, Antonella; Morisco, Anna; Gianolio, Eliana; Tesauro, Diego; Mangiapia, Gaetano; Radulescu, Aurel; Brandt, Astrid; Morelli, Giancarlo.

In: Journal of Peptide Science, Vol. 17, No. 2, 02.2011, p. 154-162.

Research output: Contribution to journalArticle

Accardo, A, Morisco, A, Gianolio, E, Tesauro, D, Mangiapia, G, Radulescu, A, Brandt, A & Morelli, G 2011, 'Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications', Journal of Peptide Science, vol. 17, no. 2, pp. 154-162. https://doi.org/10.1002/psc.1308
Accardo A, Morisco A, Gianolio E, Tesauro D, Mangiapia G, Radulescu A et al. Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications. Journal of Peptide Science. 2011 Feb;17(2):154-162. https://doi.org/10.1002/psc.1308
Accardo, Antonella ; Morisco, Anna ; Gianolio, Eliana ; Tesauro, Diego ; Mangiapia, Gaetano ; Radulescu, Aurel ; Brandt, Astrid ; Morelli, Giancarlo. / Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications. In: Journal of Peptide Science. 2011 ; Vol. 17, No. 2. pp. 154-162.
@article{6348d8c4300b4cf19375af02060fae2f,
title = "Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications",
abstract = "New mixed nanoparticles were obtained by self-aggregation of two amphiplic monomers. The first monomer (C18)2L5-Oct contains two C18 hydrophobic moieties bound to the N-terminus of the cyclic peptide octreotide, and spaced from the bioactive peptide by five units of dioxoethylene linkers. The second monomer, (C18)2DTPAGlu, (C18)2DTPA or (C18)2DOTA, and the corresponding Gd(III) complexes, contains two C18 hydrophobic moieties bound through a lysine residue to different polyamino-polycarboxy ligands: DTPAGlu, DTPA or DOTA. Mixed aggregates have been obtained and structurally characterized by small angle neutron scattering (SANS) techniques and for their relaxometric behavior. According to a decrease of negative charges in the surfactant head-group, a total or a partial micelle-to-vesicle transition is observed by passing from (C18)2DTPAGlu to (C18)2DOTA. The thicknesses of the bilayers are substantially constant, around 50 {\AA}, in the analyzed systems. Moreover, the mixed aggregates, in which a small amount of amphiphilic octreotide monomer (C18)2L5-Oct (10{\%} mol/mol) was inserted, do not differ significantly from the respective self-assembled systems. Fluorescence emission of tryptophan residue at 340 nm indicates low mobility of water molecules at the peptide surface. The proton relaxivity of mixed aggregates based on (C18)2DTPAGlu(Gd), (C18)2DTPA(Gd) and (C18)2DOTA(Gd) resulted to be 17.6, 15.2 and 10.0 mM-1 s-1 (at 20 MHz and 298K), respectively. The decrease in the relaxivity values can be ascribed to the increase in τM (81, 205 and 750 ns). The presence of amphiphilic octreotide monomer exposed on mixed aggregate surface gives the entire nanoparticles a potential binding selectivity toward somatostatin sstr2 receptor subtype, and these systems could act as MRI target-specific contrast agent. Mixed nanoparticles (micelles and liposomes) are obtained by co-aggregation of lipophilic octreotide with gadolinium complex containing amphiphilic monomers for MRI applications.",
keywords = "Amphiphilic gadolinium complexes, MRI contrast agents, Octreotide peptide, Small-angle neutron scattering, Supramolecular aggregates",
author = "Antonella Accardo and Anna Morisco and Eliana Gianolio and Diego Tesauro and Gaetano Mangiapia and Aurel Radulescu and Astrid Brandt and Giancarlo Morelli",
year = "2011",
month = "2",
doi = "10.1002/psc.1308",
language = "English",
volume = "17",
pages = "154--162",
journal = "Journal of Peptide Science",
issn = "1075-2617",
publisher = "John Wiley and Sons Ltd",
number = "2",

}

TY - JOUR

T1 - Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications

AU - Accardo, Antonella

AU - Morisco, Anna

AU - Gianolio, Eliana

AU - Tesauro, Diego

AU - Mangiapia, Gaetano

AU - Radulescu, Aurel

AU - Brandt, Astrid

AU - Morelli, Giancarlo

PY - 2011/2

Y1 - 2011/2

N2 - New mixed nanoparticles were obtained by self-aggregation of two amphiplic monomers. The first monomer (C18)2L5-Oct contains two C18 hydrophobic moieties bound to the N-terminus of the cyclic peptide octreotide, and spaced from the bioactive peptide by five units of dioxoethylene linkers. The second monomer, (C18)2DTPAGlu, (C18)2DTPA or (C18)2DOTA, and the corresponding Gd(III) complexes, contains two C18 hydrophobic moieties bound through a lysine residue to different polyamino-polycarboxy ligands: DTPAGlu, DTPA or DOTA. Mixed aggregates have been obtained and structurally characterized by small angle neutron scattering (SANS) techniques and for their relaxometric behavior. According to a decrease of negative charges in the surfactant head-group, a total or a partial micelle-to-vesicle transition is observed by passing from (C18)2DTPAGlu to (C18)2DOTA. The thicknesses of the bilayers are substantially constant, around 50 Å, in the analyzed systems. Moreover, the mixed aggregates, in which a small amount of amphiphilic octreotide monomer (C18)2L5-Oct (10% mol/mol) was inserted, do not differ significantly from the respective self-assembled systems. Fluorescence emission of tryptophan residue at 340 nm indicates low mobility of water molecules at the peptide surface. The proton relaxivity of mixed aggregates based on (C18)2DTPAGlu(Gd), (C18)2DTPA(Gd) and (C18)2DOTA(Gd) resulted to be 17.6, 15.2 and 10.0 mM-1 s-1 (at 20 MHz and 298K), respectively. The decrease in the relaxivity values can be ascribed to the increase in τM (81, 205 and 750 ns). The presence of amphiphilic octreotide monomer exposed on mixed aggregate surface gives the entire nanoparticles a potential binding selectivity toward somatostatin sstr2 receptor subtype, and these systems could act as MRI target-specific contrast agent. Mixed nanoparticles (micelles and liposomes) are obtained by co-aggregation of lipophilic octreotide with gadolinium complex containing amphiphilic monomers for MRI applications.

AB - New mixed nanoparticles were obtained by self-aggregation of two amphiplic monomers. The first monomer (C18)2L5-Oct contains two C18 hydrophobic moieties bound to the N-terminus of the cyclic peptide octreotide, and spaced from the bioactive peptide by five units of dioxoethylene linkers. The second monomer, (C18)2DTPAGlu, (C18)2DTPA or (C18)2DOTA, and the corresponding Gd(III) complexes, contains two C18 hydrophobic moieties bound through a lysine residue to different polyamino-polycarboxy ligands: DTPAGlu, DTPA or DOTA. Mixed aggregates have been obtained and structurally characterized by small angle neutron scattering (SANS) techniques and for their relaxometric behavior. According to a decrease of negative charges in the surfactant head-group, a total or a partial micelle-to-vesicle transition is observed by passing from (C18)2DTPAGlu to (C18)2DOTA. The thicknesses of the bilayers are substantially constant, around 50 Å, in the analyzed systems. Moreover, the mixed aggregates, in which a small amount of amphiphilic octreotide monomer (C18)2L5-Oct (10% mol/mol) was inserted, do not differ significantly from the respective self-assembled systems. Fluorescence emission of tryptophan residue at 340 nm indicates low mobility of water molecules at the peptide surface. The proton relaxivity of mixed aggregates based on (C18)2DTPAGlu(Gd), (C18)2DTPA(Gd) and (C18)2DOTA(Gd) resulted to be 17.6, 15.2 and 10.0 mM-1 s-1 (at 20 MHz and 298K), respectively. The decrease in the relaxivity values can be ascribed to the increase in τM (81, 205 and 750 ns). The presence of amphiphilic octreotide monomer exposed on mixed aggregate surface gives the entire nanoparticles a potential binding selectivity toward somatostatin sstr2 receptor subtype, and these systems could act as MRI target-specific contrast agent. Mixed nanoparticles (micelles and liposomes) are obtained by co-aggregation of lipophilic octreotide with gadolinium complex containing amphiphilic monomers for MRI applications.

KW - Amphiphilic gadolinium complexes

KW - MRI contrast agents

KW - Octreotide peptide

KW - Small-angle neutron scattering

KW - Supramolecular aggregates

UR - http://www.scopus.com/inward/record.url?scp=78651440633&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78651440633&partnerID=8YFLogxK

U2 - 10.1002/psc.1308

DO - 10.1002/psc.1308

M3 - Article

C2 - 21234988

AN - SCOPUS:78651440633

VL - 17

SP - 154

EP - 162

JO - Journal of Peptide Science

JF - Journal of Peptide Science

SN - 1075-2617

IS - 2

ER -