Peptide Derivatized Lamellar Aggregates as Target‐Specific MRI Contrast Agents

Tesauro, Diego; Accardo, Antonella; Gianolio, Eliana; Paduano, Luigi; Teixeira, J.; Schillén, Karin; Aime, Silvio; Morelli, Giancarlo

doi:10.1002/cbic.200700077

Cited by 24 publications

(42 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the mixed aggregates the molar ratio between the two monomers plays a crucial role in the assembly process. [15] In this study we fixed pH at physiological levels (pH 7.4), and the molar ratio between the monomers ((C18) 2 DTPAGlu/A C H T U N G T R E N N U N G (C18) 2 PEG 2000 CCK8) at 70:30). To characterize the supramolecular aggregates obtained by mixing the two synthetic monomers, a fully structural characterization was carried out by using several physicochemical techniques.…”

Section: Resultsmentioning

confidence: 99%

“…As already reported for other mixed aggregate systems, [15] receptor binding ability can be evaluated by standard nuclear medicine experiments. Radiolabeling of the aggregates was performed at concentrations above critical micellar concentration to avoid the presence of free monomers in solution.…”

Section: In Vitro Biological Assaysmentioning

confidence: 99%

“…With this strategy, we have recently developed mixed aggregate systems, acting as high relaxivity MRI contrast agents, [13][14][15] formed by two different amphiphilic monomers, one containing a bioactive peptide and the other a chelating moiety capable of forming stable complexes with GdA C H T U N G T R E N N U N G (III) ions.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Peptide‐Containing Aggregates as Selective Nanocarriers for Therapeutics

et al. 2008

Self Cite

View full text Add to dashboard Cite

New nanocarriers are obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-111 complexes linked to the same hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of approximately 40 A and length >700 A, open bilayer fragments with thickness approximately 65 A, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: In Vitro Biological Assaysmentioning

confidence: 99%

See 1 more Smart Citation

Peptide‐Containing Aggregates as Selective Nanocarriers for Therapeutics

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Self-assembling micelles of MonY(Gd) present high relaxivity values (r 1p = 15.03 mm terized by the presence of a large amount of gadolinium complex and of several molecules of CCK8 bioactive peptide exposed on their surface. [12][13][14] These aggregates are obtained by combining two different molecules, one containing the gadolinium complex covalently bound to a hydrophobic moiety and the other containing the CCK8 bioactive peptides linked, through a polyoxyethylene spacer, to a similar hydrophobic moiety. When assembled together at the desired molar ratio, we obtained aggregates with different shapes and sizes, such as spherical micelles, rodlike micelles, open bilayer structures, and vesicles.…”

Section: Introductionmentioning

confidence: 99%

Structural and Relaxometric Characterization of Peptide Aggregates Containing Gadolinium Complexes as Potential Selective Contrast Agents in MRI

et al. 2007

Self Cite

View full text Add to dashboard Cite

The structural and relaxometric characterization of a novel class of supramolecular aggregates, as potential tumor-specific contrast agents in magnetic resonance imaging (MRI), is reported. The aggregates are based on a new monomer with an upsilon shape (MonY) that contains, in the same molecule, all three fundamental tasks that are required: 1) a hydrophobic moiety that allows the formation of supramolecular aggregates; 2) the bioactive CCK8 peptide for target recognition; and 3) a chelating agent able to give stable gadolinium complexes. As indicated by dynamic light scattering and small-angle neutron scattering (SANS) measurements, MonY and its gadolinium complex MonY(Gd) aggregate in aqueous solution to give ellipsoidal micelles with a ratio between the micellar axes of approximately 1.7 and an aggregation number N(agg) of approximately 30. There are no differences in the aggregation behavior of MonY and MonY(Gd), which indicates that the presence of metal ions, and therefore the reduction of the net charge, does not influence the aggregation behavior. When MonY or MonY(Gd) are blended with dioleoyl phosphatidylcholine (DOPC), the aggregation behavior is dictated by the tendency of DOPC to give liposomes. Only when the amount of MonY or MonY(Gd) is higher than 20 % is the coexistence of liposomes and micelles observed. The thickness d of the bilayer is estimated by SANS to be approximately 35-40 A, whereas cryogenic transmission electron microscopy images show that the diameter of the liposomes ranges from approximately 50 to 150 nm. Self-assembling micelles of MonY(Gd) present high relaxivity values (r(1p)=15.03 mM(-1) s(-1)) for each gadolinium complex in the aggregate. Liposomes containing MonY(Gd) inserted in the DOPC bilayer at a molar ratio of 20:80 present slightly lower relaxivity values (r(1p)=12.7 mM(-1) s(-1)), independently of their internal or external position in the liposome.

show abstract

“…Then, the resin was washed three times with DCM and three times with DMF, and N,N-dioctadecylsuccinamic acid (0.249 g, 0.4 mmol) was coupled according to the previously published procedure. 23 The Fmoc-Lys(Fmoc)-OH residue was coupled successively on the principal chain. The two Fmoc protecting groups, on the N α and N ε , were then simultaneously removed by washing the resin five times with 30% piperidine in DMF (v/v) for 10 min.…”

mentioning

confidence: 99%

Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

Ringhieri¹,

Mannucci²,

Conti³

et al. 2017

IJN

Self Cite

View full text Add to dashboard Cite

Mixed liposomes, obtained by coaggregation of 1,2-dioleoyl-sn-glycero-3-phosphocholine and of the synthetic monomer containing a gadolinium complex ([C18]2DTPA[Gd]) have been prepared. Liposomes externally decorated with KCCYSL (P6.1 peptide) sequence in its monomeric, dimeric, and tetrameric forms are studied as target-selective delivery systems toward cancer cells overexpressing human epidermal growth factor receptor-2 (HER-2) receptors. Derivatization of liposomal surface with targeting peptides is achieved using the postmodification method: the alkyne-peptide derivative Pra-KCCYSL reacts, through click chemistry procedures, with a synthetic surfactant modified with 1, 2, or 4 azido moieties previously inserted in liposome formulation. Preliminary in vitro data on MDA-MB-231 and BT-474 cells indicated that liposomes functionalized with P6.1 peptide in its tetrameric form had better binding to and uptake into BT-474 cells compared to liposomes decorated with monomeric or dimeric versions of the P6.1 peptide. BT-474 cells treated with liposomes functionalized with the tetrameric form of P6.1 showed high degree of liposome uptake, which was comparable with the uptake of anti-HER-2 antibodies such as Herceptin. Moreover, magnetic MRI experiments have demonstrated the potential of liposomes to act as MRI contrast agents

show abstract

Peptide Derivatized Lamellar Aggregates as Target‐Specific MRI Contrast Agents

Cited by 24 publications

References 32 publications

Peptide‐Containing Aggregates as Selective Nanocarriers for Therapeutics

Peptide‐Containing Aggregates as Selective Nanocarriers for Therapeutics

Structural and Relaxometric Characterization of Peptide Aggregates Containing Gadolinium Complexes as Potential Selective Contrast Agents in MRI

Liposomes derivatized with multimeric copies of KCCYSL peptide as targeting agents for HER-2-overexpressing tumor cells

Contact Info

Product

Resources

About