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Dive into the research topics where Antonella Accardo is active.

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Featured researches published by Antonella Accardo.


Chemistry: A European Journal | 2011

Clickable Functionalization of Liposomes with the gH625 Peptide from Herpes simplex Virus Type I for Intracellular Drug Delivery

Rossella Tarallo; Antonella Accardo; Annarita Falanga; Daniela Guarnieri; Giuseppe Vitiello; Paolo A. Netti; Gerardino D'Errico; Giancarlo Morelli; Stefania Galdiero

Liposomes externally modified with the nineteen residues gH625 peptide, previously identified as a membrane-perturbing domain in the gH glycoprotein of Herpes simplex virus type I, have been prepared in order to improve the intracellular uptake of an encapsulated drug. An easy and versatile synthetic strategy, based on click chemistry, has been used to bind, in a controlled way, several copies of the hydrophobic gH625 peptide on the external surface of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPG)-based liposomes. Electron paramagnetic resonance studies, on liposomes derivatized with gH625 peptides, which are modified with the 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid (TOAC) spin label in several peptide positions, confirm the positioning of the coupled peptides on the liposome external surface, whereas dynamic light scattering measurements indicate an increase of the diameter of the liposomes of approximately 30% after peptide introduction. Liposomes have been loaded with the cytotoxic drug doxorubicin and their ability to penetrate inside cells has been evaluated by confocal microscopy experiments. Results suggest that liposomes functionalized with gH625 may act as promising intracellular targeting carriers for efficient delivery of drugs, such as chemotherapeutic agents, into tumor cells.


Polymer Journal | 2013

Peptide-based targeting strategies for simultaneous imaging and therapy with nanovectors

Antonella Accardo; Diego Tesauro; Giancarlo Morelli

Theranostic agents based on nanovectors (liposomes, naposomes, micelles, polymeric micelles and micelles built around a solid core) able to carry, simultaneously, a drug and a contrast agent and externally modified with targeting peptides are described.


International Journal of Nanomedicine | 2014

Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs.

Antonella Accardo; Luigi Aloj; Michela Aurilio; Giancarlo Morelli; Diego Tesauro

Active targeting by means of drug encapsulated nanoparticles decorated with targeting bioactive moieties represents the next frontier in drug delivery; it reduces drug side effects and increases the therapeutic index. Peptides, based on their chemical and biological properties, could have a prevalent role to direct drug encapsulated nanoparticles, such as liposomes, micelles, or hard nanoparticles, toward the tumor tissues. A considerable number of molecular targets for peptides are either exclusively expressed or overexpressed on both cancer vasculature and cancer cells. They can be classified into three wide categories: integrins; growth factor receptors (GFRs); and G-protein coupled receptors (GPCRs). Therapeutic agents based on nanovectors decorated with peptides targeting membrane receptors belonging to the GPCR family overexpressed by cancer cells are reviewed in this article. The most studied targeting membrane receptors are considered: somatostatin receptors; cholecystokinin receptors; receptors associated with the Bombesin like peptides family; luteinizing hormone-releasing hormone receptors; and neurotensin receptors. Nanovectors of different sizes and shapes (micelles, liposomes, or hard nanoparticles) loaded with doxorubicin or other cytotoxic drugs and externally functionalized with natural or synthetic peptides are able to target the overexpressed receptors and are described based on their formulation and in vitro and in vivo behaviors.


International Journal of Nanomedicine | 2012

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

Antonella Accardo; Giuseppina Salsano; Anna Morisco; Michela Aurilio; Antonio Parisi; Francesco Maione; Carla Cicala; Diego Tesauro; Luigi Aloj; Giuseppe De Rosa; Giancarlo Morelli

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 C18 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.


Journal of Peptide Science | 2009

Micelles derivatized with octreotide as potential target-selective contrast agents in MRI†‡

Anna Morisco; Antonella Accardo; Eliana Gianolio; Diego Tesauro; Ettore Benedetti; Giancarlo Morelli

New amphiphilic monomers (OCA‐DTPAGlu and OCA‐DOTA) containing, in the same molecule, three different functions: (i) the chelating agent (DTPAGlu or DOTA) able to coordinate gadolinium ion, (ii) the octreotide bioactive peptide able to target somatostatin receptors, and (iii) a hydrophobic moiety with two 18‐carbon atoms alkyl chains have been designed and synthesized by solid‐phase methods. The novel amphiphilic monomers aggregate, in water solution, giving stable micelles at very low concentration (cmc values of 2.3 × 10−6 mol kg−1 and 2.5 × 10−6 mol kg−1 for OCA‐DTPAGlu and OCA‐DOTA, respectively) as confirmed by fluorescence spectroscopy. Fluorescence studies and circular dichroism experiments indicate, for the two compounds as well as for their gadolinium complexes (OCA‐DOTA(Gd) and OCA‐DTPAGlu(Gd)), the complete exposure of octreotide on the micelle surface, and the predominant presence of an antiparallel β‐sheet peptide conformation characterized by a β‐like turn. The high relaxivity value (r1p = 13.9 mM−1 s−1 at 20 MHz and 25 °C), measured for micelles obtained by the gadolinium complex OCA‐DTPAGlu(Gd), indicates these aggregates as promising target‐selective magnetic resonance imaging (MRI) contrast agents. Copyright


ChemMedChem | 2011

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

Chiara Falciani; Antonella Accardo; Jlenia Brunetti; Diego Tesauro; Barbara Lelli; Alessandro Pini; Luisa Bracci; Giancarlo Morelli

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, NT4Lys(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‐NT4Lys(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‐NT4Lys(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‐NT4Lys(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.


Molecular BioSystems | 2010

Peptide modified nanocarriers for selective targeting of bombesin receptors

Antonella Accardo; Rosalba Mansi; Anna Morisco; Gaetano Mangiapia; Luigi Paduano; Diego Tesauro; Aurel Radulescu; Michela Aurilio; Luigi Aloj; Claudio Arra; Giancarlo Morelli

The present work describes new supramolecular aggregates obtained by co-assembling two different amphiphilic molecules, one containing the bioactive bombesin peptide (BN), or a scramble sequence, and the other, the DOTA chelating agent, (C18)(2)DOTA, capable of forming stable complexes with the radioactive (111)In(III) isotope. The peptide in the amphiphilic monomer is spaced by the lipophilic moiety through ethoxylic spacers of different length: a shorter spacer with five units of dioxoethylene moieties in (C18)(2)L5-peptide, or a longer spacer consisting of a Peg3000 residue in (C18)(2)Peg3000-peptide. Structural characterization by SANS and DLS techniques indicates that, independently from the presence of the peptide containing monomer in the final composition, the predominant aggregates are liposomes of similar shape and size with a hydrodynamic radius R(h) around 200 nm and bilayer thickness, d, of 4 nm. In vitro data show specific binding of the (111)In-(C18)(2)DOTA/(C18)(2)L5-[7-14]BN 90:10 liposomes in receptor expressing cells. However, the presence of the Peg3000 unit on the external liposomal surface, could hide the peptide and prevent the receptor binding. In vivo experiments using (111)In-(C18)(2)DOTA/(C18)(2)L5-[7-14]BN show the expected biological behavior of aggregates of such size and molecular composition, moreover there is an increase in concentration of the GRPR targeting aggregate in the tumors compared to control at the 48 h time point evaluated (2.4% ID/g versus 1.6% ID/g).


ChemMedChem | 2008

Peptide-containing aggregates as selective nanocarriers for therapeutics

Antonella Accardo; Diego Tesauro; Luigi Aloj; Laura Tarallo; Claudio Arra; Gaetano Mangiapia; Mauro Vaccaro; Carlo Pedone; Luigi Paduano; Giancarlo Morelli

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 ∼40 Å and length >700 Å, open bilayer fragments with thickness ∼65 Å, 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.


ChemBioChem | 2007

Peptide derivatized lamellar aggregates as target-specific MRI contrast agents.

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

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 of∼80–100 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.


Journal of Peptide Science | 2011

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

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. Copyright

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Giancarlo Morelli

University of Naples Federico II

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Diego Tesauro

University of Naples Federico II

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Luigi Paduano

University of Naples Federico II

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Paola Ringhieri

University of Naples Federico II

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Carlo Diaferia

University of Naples Federico II

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Gaetano Mangiapia

University of Naples Federico II

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Anna Morisco

University of Naples Federico II

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Luigi Aloj

University of Naples Federico II

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Carlo Pedone

University of Naples Federico II

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