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High-relaxivity supramolecular aggregates containing peptides and Gd complexes as contrast agents in MRI

Accardo, Antonella; Tesauro, Diego; Gianolio, Eliana; Morelli, Giancarlo; Aime, Silvio; Vaccaro, Mauro; Mangiapia, Gaetano; Paduano, Luigi and Schillén, Karin LU (2007) In Journal of Biological Inorganic Chemistry 12(2). p.267-276
Abstract
Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C18H37)2NCO(CH2)2CO(AdOO)5-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C18H37)2NCO(CH2)2COLys(DTPAGlu)CONH2 (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-l-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are observed at physiological ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the... (More)
Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C18H37)2NCO(CH2)2CO(AdOO)5-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C18H37)2NCO(CH2)2COLys(DTPAGlu)CONH2 (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-l-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are observed at physiological ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the repulsions between the polar heads and among the aggregates in solution, thus supporting the formation of large-curvature aggregates such as bilayer structures like vesicles. In these conditions the closed, vesicular shape and the large size (hydrodynamic radius of about 300 Å) of the aggregates allow a high number of paramagnetic gadolinium complexes and bioactive peptides to be accommodated on the inner and external surfaces . The presence of the salt causes a variation in the structural arrangement of the molecules and a partial rigidification of the assembled Gd(III) complexes on the surface vesicles, reducing their internal motions and giving an approximately 15% higher relaxivity value (r 1p = 21.0 and 18.6 Mm−1 s−1 in the presence and in the absence of NaCl, respectively). The vesicles obtained, for the high relaxivity of each gadolidium complex and for the presence of a surface-exposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Supramolecular aggregates - Gadolinium complexes - Magnetic resonance imaging - C-terminal octapeptide of cholecystokinin - Dynamic light scattering
in
Journal of Biological Inorganic Chemistry
volume
12
issue
2
pages
267 - 276
publisher
Springer
external identifiers
  • wos:000243905800012
  • scopus:33846669975
ISSN
1432-1327
DOI
10.1007/s00775-006-0186-6
language
English
LU publication?
yes
id
ded8ce04-ecec-4cf4-a856-8698f2c88100 (old id 608939)
date added to LUP
2007-12-03 11:01:07
date last changed
2017-01-01 04:54:22
@article{ded8ce04-ecec-4cf4-a856-8698f2c88100,
  abstract     = {Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C18H37)2NCO(CH2)2CO(AdOO)5-G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C18H37)2NCO(CH2)2COLys(DTPAGlu)CONH2 (DTPAGlu is N,N-bis[2-[bis(carboxyethyl)amino]ethyl]-l-glutamic acid), are characterized for their structural parameters by dynamic light scattering and for their relaxometric properties, in the absence and in the presence of 0.9 wt% NaCl. Two different aggregates (micelles and bilayer structures) are present in the absence of NaCl, while only bilayer structures are observed at physiological ionic strength. The presence of NaCl increases the ionic strength, promoting a decrease in the repulsions between the polar heads and among the aggregates in solution, thus supporting the formation of large-curvature aggregates such as bilayer structures like vesicles. In these conditions the closed, vesicular shape and the large size (hydrodynamic radius of about 300 Å) of the aggregates allow a high number of paramagnetic gadolinium complexes and bioactive peptides to be accommodated on the inner and external surfaces . The presence of the salt causes a variation in the structural arrangement of the molecules and a partial rigidification of the assembled Gd(III) complexes on the surface vesicles, reducing their internal motions and giving an approximately 15% higher relaxivity value (r 1p = 21.0 and 18.6 Mm−1 s−1 in the presence and in the absence of NaCl, respectively). The vesicles obtained, for the high relaxivity of each gadolidium complex and for the presence of a surface-exposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents.},
  author       = {Accardo, Antonella and Tesauro, Diego and Gianolio, Eliana and Morelli, Giancarlo and Aime, Silvio and Vaccaro, Mauro and Mangiapia, Gaetano and Paduano, Luigi and Schillén, Karin},
  issn         = {1432-1327},
  keyword      = {Supramolecular aggregates - Gadolinium complexes - Magnetic resonance imaging - C-terminal octapeptide of cholecystokinin - Dynamic light scattering},
  language     = {eng},
  number       = {2},
  pages        = {267--276},
  publisher    = {Springer},
  series       = {Journal of Biological Inorganic Chemistry},
  title        = {High-relaxivity supramolecular aggregates containing peptides and Gd complexes as contrast agents in MRI},
  url          = {http://dx.doi.org/10.1007/s00775-006-0186-6},
  volume       = {12},
  year         = {2007},
}