| 1. |
- Accardo, Antonella, et al.
(författare)
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High-relaxivity supramolecular aggregates containing peptides and Gd complexes as contrast agents in MRI
- 2007
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Ingår i: Journal of Biological Inorganic Chemistry. - : Springer Science and Business Media LLC. - 1432-1327 .- 0949-8257. ; 12:2, s. 267-276
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Luchini, Alessandra, et al.
(författare)
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Neutron Reflectometry reveals the interaction between functionalized SPIONs and the surface of lipid bilayers
- 2017
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Ingår i: Colloids and Surfaces B. - : ELSEVIER SCIENCE BV. - 0927-7765 .- 1873-4367. ; 151, s. 76-87
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Tidskriftsartikel (refereegranskat)abstract
- The safe application of nanotechnology devices in biomedicine requires fundamental understanding on how they interact with and affect the different components of biological systems. In this respect, the cellular membrane, the cell envelope, certainly represents an important target or barrier for nanosystems. Here we report on the interaction between functionalized SuperParamagnetic Iron Oxide Nanoparticles (SPIONs), promising contrast agents for Magnetic Resonance Imaging (MRI), and lipid bilayers that mimic the plasma membrane. Neutron Reflectometry, supported by Quartz Crystal Microbalance with Dissipation monitoring (QCM-D) experiments, was used to characterize this interaction by varying both SPION coating and lipid bilayer composition. In particular, the interaction of two different SPIONs, functionalized with a cationic surfactant and a zwitterionic phospholipid, and lipid bilayers, containing different amount of cholesterol, were compared. The obtained results were further validated by Dynamic Light Scattering (DLS) measurements and Cryogenic Transmission Electron Microscopy (Cryo-TEM) images. None of the investigated functionalized SPIONs were found to disrupt the lipid membrane. However, in all case we observed the attachment of the functionalized SPIONs onto the surface of the bilayers, which was affected by the bilayer rigidity, i.e. the cholesterol concentration.
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| 3. |
- Mangiapia, Gaetano, et al.
(författare)
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Cubosomes for ruthenium complex delivery: formulation and characterization
- 2011
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Ingår i: Soft Matter. - : Royal Society of Chemistry (RSC). - 1744-6848 .- 1744-683X. ; 7:22, s. 10577-10580
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Tidskriftsartikel (refereegranskat)abstract
- An amphiphilic ruthenium-based molecule (DOPURu) with potential antineoplastic activity has been synthesized, and its aggregation behavior in the presence of phospholipids has been investigated. A very rich variety of aggregates has been found, spanning from vesicles to cubic bicontinuous phases. Cubosomes here presented represent one of the first systems with potential use for medical therapy.
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| 4. |
- Tesauro, Diego, et al.
(författare)
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Peptide Derivatized Lamellar Aggregates as Target-Specific MRI Contrast Agents
- 2007
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227 .- 1439-7633. ; 8:8, s. 950-955
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Tidskriftsartikel (refereegranskat)abstract
- The relaxivity behaviour and the structural characterization of new supramolecular aggregates (bilayer structures and micelles) obtained by combining two different amphiphilic monomers are reported. One monomer, (C18)2DTPAGlu-Gd, contains a very stable gadolinium complex, and the other, DSPE-PEG2000-CCK8, contains the bioactive CCK8 peptide. Samples that contained only DSPE-PEG2000-CCK8, or up to 50 % (C18)2DTPAGlu-Gd, aggregated as double-layer structures (lamellar aggregates) with a thickness of80-100 Å, as evaluated by SANS measurement and Cryo-TEM imaging. A transition to micelle formation was observed when the amount of (C18)2DTPAGlu-Gd in the aggregate was increased. These were rod-like micelles 40 Å in radius and >200 Å in length. The proton relaxivities for both lamellar aggregates and rod-like micelles were the same (17.2 mM-1 s-1), although the values were the results of different combinations of local and global contributions. The in vitro target selectivity of aggregates that contained the CCK-8 peptide was demonstrated by using nuclear medicine techniques.
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| 5. |
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| 6. |
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| 7. |
- Vaccaro, Mauro, et al.
(författare)
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Peptide and Gd Complexes Containing Colloidal Assemblies as Tumor-Specific Contrast Agents in MRI: Physicochemical Characterization
- 2007
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Ingår i: Biophysical Journal. - : Elsevier BV. - 1542-0086 .- 0006-3495. ; 93:5, s. 1736-1746
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Tidskriftsartikel (refereegranskat)abstract
- The aggregation behavior of an amphiphilic supramolecular system, with potential application as a tumor-specific magnetic resonance imaging contrast agent, has been studied in detail by dynamic light scattering, small-angle neutron scattering and cryotransmission electron microscopy. The system was constituted of mixed aggregates formed by an anionic unimer containing the DTPAGlu, a chelating agent for the paramagnetic Gd3+ ion, and an uncharged unimer containing the bioactive peptide CCK8, capable of directing the assembly toward tumor cells. Mixed aggregates formed by both unimers, and in the case of the DTPAGlu unimer with the chelating agent as free base or as Gd3+ complex, have been investigated. A number of interesting features of the aggregation behavior were revealed: at physiological pH, micelles and bilayer structures were present, whereas upon decreasing solution pH or increasing ionic strength, the formation of bilayer structures was favored. On the basis of the above observations, the aggregating mechanism has been elucidated by considering the screening effect on intra- and interaggregate electrostatic repulsions.
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| 8. |
- Vaccaro, Mauro, et al.
(författare)
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Supramolecular aggregates of amphiphilic gadolinium complexes as blood pool MRI/MRA contrast agents: Physicochemical characterization
- 2006
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 22:15, s. 6635-6643
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Tidskriftsartikel (refereegranskat)abstract
- In this paper, we present the development of a new potential blood pool contrast agent for magnetic resonance imaging applications (MRA/MRI) based on gadolinium complexes containing amphiphilic supramolecular aggregates. A novel amphiphilic unimer, containing the DTPAGlu chelating agent covalently bound to two C18 alkylic chains, has been synthesized. DTPAGlu is a well-known chelating agent for a wide number of ions such as the paramagnetic metal ion Gd3+ used as contrast agent in MRA/MRI. The wide aggregation behavior of this surfactant, as free base or as gadolinium complex, has been studied and compared by means of dynamic light scattering, small-angle neutron scattering and cryogenic transmission electron microscopy techniques. Near neutral pH in both cases, the dominant aggregates are micelles. The high negative actual charge of the surfactant headgroup causes a strong headgroups repulsion, promoting the formation of large and high curvature aggregates. By decreasing pH and less markedly increasing the ionic strength, we observe a micelle-to-vesicle transition driven by a decreased electrostatic repulsion. A straightforward switch between different aggregation states can be particularly useful in the development of pH-responsive MRA/MRI contrast agents.
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