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

Vaccaro, Mauro; Mangiapia, Gaetano; Paduano, Luigi; Gianolio, Eliana; Accardo, Antonella; Tesauro, Diego; Morelli, Giancarlo

doi:10.1002/cphc.200700505

Cited by 42 publications

(64 citation statements)

References 41 publications

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“…[28] Briefly, monomers were dissolved in a choloroform/methanol mixture, and the solvent was subsequently evaporated. The resulting film was hydrated in 0.1 m buffered solution (pH 7.4) at room temperature.…”

Section: Aggregate Formation and Dlsmentioning

confidence: 99%

“…[29] Mixed liposomes in which a small amount (5 %) of NT peptide derivative is added to the DOPC phospholipid have similar liposomal structure and dimension to pure DOPC liposomes, as already demonstrated for pure and mixed aggregates based on similar amphiphilic monomers. [28] Doxorubicin loading and release Doxorubicin (Doxo) was loaded into the liposome using the pH gradient method. [30] Liposomes were prepared at pH 4.0, and phosphate buffer was diluted to 2.5 mm because of the poor solubility of doxorubicin in phosphate solution with the pH range 5.0-8.5.…”

Section: Aggregate Formation and Dlsmentioning

confidence: 99%

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Target‐Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides

et al. 2011

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The structure and the in vitro behavior of liposomes filled with the cytotoxic drug doxorubicin (Doxo) and functionalized on the external surface with a branched moiety containing four copies of the 8-13 neurotensin (NT) peptide is reported. The new functionalized liposomes, DOPC-NT₄Lys(C₁₈)₂, are obtained by co-aggregation of the DOPC phospholipid with a new synthetic amphiphilic molecule, NT₄ Lys(C₁₈)₂, which contains a lysine scaffold derivatized with a lipophilic moiety and a tetrabranched hydrophilic peptide, NT8-13, a neurotensin peptide fragment well known for its ability to mimic the neurotensin peptide in receptor binding ability. Dynamic light scattering measurements indicate a value for the hydrodynamic radius (RH) of 88.3±4.4 nm. The selective internalization and cytotoxicity of DOPC-NT₄ Lys(C₁₈)₂ liposomes containing Doxo, as compared to pure DOPC liposomes, were tested in HT29 human colon adenocarcinoma and TE671 human rhabdomyosarcoma cells, both of which express neurotensin receptors. Peptide-functionalized liposomes show a clear advantage in comparison to pure DOPC liposomes with regard to drug internalization in both HT29 and TE671 tumor cells: FACS analysis indicates an increase in fluorescence signal of the NT₄-liposomes, compared to the DOPC pure analogues, in both cell lines; cytotoxicity of DOPC-NT₄ Lys(C₁₈)₂-Doxo liposomes is increased four-fold with respect to DOPC-Doxo liposomes in both HT29 and TE671 cell lines. These effects could to be ascribed to the higher rate of internalization for DOPC-NT₄ Lys(C₁₈)₂-Doxo liposomes, due to stronger binding driven by a lower dissociation constant of the NT₄-liposomes that bind the membrane onto a specific protein, in contrast to DOPC liposomes, which approach the plasma membrane unselectively.

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Section: Aggregate Formation and Dlsmentioning

confidence: 99%

Section: Aggregate Formation and Dlsmentioning

confidence: 99%

Target‐Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides

et al. 2011

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“…22 An alternative strategy in which the chelating agent, the reporter peptide and the hydrophobic hydrocarbon moiety are placed together on the same amphiphilc moiety, has been also successfully used. 18 In all cases the nanoparticles obtained (spherical micelles, elongated micelles, or liposomes) are characterized by the presence of the bioactive peptide well exposed on the external surface of the aggregate and by the presence of the anionic chelating agent on the aggregate shell. The target selectivity has been studied in vitro and in vivo by labelling the aggregates with the gamma emitting isotope 111 In that is firmly complexed by the chelating agents.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2011

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New liposomal aggregates, prepared by combining together, in a 90:10 molar ratio, two amphiphilic monomers, one containing two hydrocarbon chains in the hydrophobic region and the anionic DOTA chelating agent as hydrophilic moiety, and the other containing the same hydrophobic moiety and the CCK8 peptide, are described. The liposomal aggregates because of the presence of the specific moiety, constituted by the CCK8 peptide, which selectively recognizes CCK receptors on tumor cells are used as drug carriers with the aim to deliver into tumor cells the appropriate antitumor drug. The drug loading content and the releasing properties of the liposomal aggregates are studied by the use of the cytotoxic doxorubicin as drug model. The doxorubicin loading content determination reveals that above 95% of the total drug was uptaken with a corresponding drug/lipid w/w ratio of 0.134. The cellular uptake of the targeted liposomal doxorubicin with respect to the self-assembled, nonspecific, liposomal doxorubicin is evaluated using flow cytometry assays. The doxorubicin cell content for two types of cell systems, namely, A431 and HuVEC cells, for peptide derivatized liposomes was 70- and 8-fold higher, respectively, than for nontargeted liposomes, indicating that the bioactive CCK8 peptide is able to enhance the doxorubicin uptake into the carcinoma cells in vitro. The cytotoxicity effect of liposomal doxorubicin on A431 cells has been assessed by MTT assays: in presence of drug amounts ranged between 250 and 1000 ng/ml, incubation with peptide derivatized liposomes showed significantly lower cell survival compared with nontargeted liposomes.

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“…Moreover, the authors also studied liposomes prepared by co-aggregation of a synthetic amphiphilic monomer containing both the bioactive peptide and the chelating agent, with commercial phospholipids. In both cases, targeted nanocarriers engineered to conjugate imaging and therapeutic functions [20][21][22][23][24] were obtained for potential theranostic applications. Derivatized nanosystems, capable of diagnosis, drug delivery, and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine.…”

Section: Introductionmentioning

confidence: 99%

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

Accardo

Salsano

Morisco

et al. 2012

IJN

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Objectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C 18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. Conclusion:The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.

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

Cited by 42 publications

References 41 publications

Target‐Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides

Target‐Selective Drug Delivery through Liposomes Labeled with Oligobranched Neurotensin Peptides

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

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

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