Giancarlo Morelli | Università degli Studi di Napoli "Federico II" (original) (raw)

Papers by Giancarlo Morelli

Characterization of a multicomponent aggregate containing a bio-active peptide and a Gd complex

Biophysical Journal, 2007

The aggregation behavior of an amphiphilic supramolecular system, with potential application as a... more 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 Gd 31 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 Gd 31 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.

Journal of Peptide Science, 2008

The chemical synthesis by solid-phase methods of a novel amphiphilic peptide, peptide-conjugate a... more The chemical synthesis by solid-phase methods of a novel amphiphilic peptide, peptide-conjugate amphiphile (PCA), containing in the same molecule three different functions: (i) the N ,N -bis[2-[bis(carboxy-ethyl)amino]ethyl]-L-glutamic acid (DTPAGlu) chelating agent, (ii) the CCK8 bioactive peptide, and (iii) a hydrophobic moiety containing four alkyl chains with 18 carbon atoms each, is reported. In water solution at pH 7.4, PCA self-assembles in very stable micelles at very low concentration [critical micellar concentration (cmc) values of 5 × 10 −7 mol kg −1 ] as confirmed by fluorescence spectroscopy. The structural characterization, obtained with small-angle neutron scattering (SANS) measurements, indicates that the aggregates are substantially represented by ellipsoidal micelles with an aggregation number of 39 ± 2 and the two micellar axes of about 52 and 26Å.

Micelles obtained by aggregation of gemini surfactants containing the CCK8 peptide and a gadolinium complex

Journal of Biological Inorganic Chemistry, 2009

Two gemini surfactants, [C18CysL5CCK8]2 and [C18CysDTPAGlu]2, containing, respectively, the CCK8 ... more Two gemini surfactants, [C18CysL5CCK8]2 and [C18CysDTPAGlu]2, containing, respectively, the CCK8 peptide and the DTPAGlu chelating agent or its gadolinium complex have been prepared by linking lipophilic chains through a disulfide bond between two cysteine residues. The two surfactants aggregate in water solution forming pure or mixed micelles, with a critical micellar concentration in the 5 × 10−6–5 × 10−5 mol kg−1 range, as measured by fluorescence

JBIC Journal of Biological Inorganic Chemistry, 2007

Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C 18 H... more Mixed supramolecular aggregates, obtained by assembling together two amphiphilic monomers (C 18 H 37 ) 2 NCO(CH 2 ) 2 CO(AdOO) 5 -G-CCK8 (AdOO is 8-amino-3,6-dioxaoctanoic acid, CCK8 is C-terminal octapeptide of cholecystokinin) and (C 18 H 37 ) 2 NCO (CH 2 ) 2 COLys(DTPAGlu)CONH 2 (DTPAGlu is N,Nbis[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 surfaceexposed bioactive peptide, are very promising candidates as target-selective MRI contrast agents.

Supramolecular Aggregates of Amphiphilic Gadolinium Complexes as Blood Pool MRI/MRA Contrast Agents: Physicochemical Characterization

Langmuir, 2006

Peptide modified nanocarriers for selective targeting of bombesin receptors

Molecular BioSystems, 2010

The present work describes new supramolecular aggregates obtained by co-assembling two different ... more 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).

Octreotide labeled aggregates containing platinum complexes as nanovectors for drug delivery

The synthesis, formulation and a complete physico-chemical characterization, by dynamic light sca... more The synthesis, formulation and a complete physico-chemical characterization, by dynamic light scattering and small angle neutron scattering techniques, of new liposomal aggregates obtained by co-assembling an amphiphilic molecule containing a platinum complex, Peg1500 -Lys(Pt-aminoEtGly)-Lys(C18)2, (abbreviated as (C18)2-PKAG-Pt), with a second amphiphilic monomer, (C18H37)2NCO(CH2)2CO(AdOO)5-Oct ((C18)2 L5-Oct), containing the octreotide bioactive peptide, is reported. Liposomes of (C18)2-PKAG-Pt present a radius of 48 nm, whereas the mixed aggregates (C18)2-PKAG-Pt/(C18)2L5-Oct at 90/10 M ratio give larger liposomes with a radius of 84 nm. In both cases, the bilayer thickness is ~5.3 nm. Encapsulation of doxorubicin in mixed liposomes is also obtained by using the pH gradient method. The obtained liposomes could represent a new target selective cargo system for delivery of cisplatin based drugs and/or doxorubicin on cells overexpressing the sstr2 and sstr5 somatostatin receptors.

Colloid and Polymer Science, 2008

Two novel amphiphilic unimers containing an aliphatic hydrophobic chain (PDA) with two C≡C triple... more Two novel amphiphilic unimers containing an aliphatic hydrophobic chain (PDA) with two C≡C triple bonds and hydrophilic heads presenting the chelating agent DTPAGlu and the CCK8 bioactive peptide, respectively, have been prepared by solid phase synthesis. Aggregates obtained by mixing together PDA-DTPAGlu, or its Gd(III) complex, and PDA-L2-CCK8 in 70/30 molar ratio before and after a polymerization process carried out by UV irradiation have been structurally characterized by means of small angle neutron scattering. The relaxivity properties of aggregates containing Gadolinium complexes have also been investigated. Elongated mixed micelles have been observed, in which the relaxivity value r 1p for each Gadolinium complex, measured at 20 MHz and 298 K, is around 12 mM -1 s -1 .

Physicochemical Properties of Mixed Micellar Aggregates Containing CCK Peptides and Gd Complexes Designed as Tumor Specific Contrast Agents in MRI †

Journal of the American Chemical Society, 2004

New amphiphilic molecules containing a bioactive peptide or a claw moiety have been prepared in o... more New amphiphilic molecules containing a bioactive peptide or a claw moiety have been prepared in order to obtain mixed micelles as target-specific contrast agents in magnetic resonance imaging. The first molecule, C(18)H(37)CONH(AdOO)(2)-G-CCK8 (C18CCK8), contains a C18 hydrophobic moiety bound to the C-terminal cholecystokinin octapeptide amide (CCK 26-33 or CCK8). The second amphiphilic compound, C(18)H(37)CONHLys(DTPAGlu)CONH(2) (C18DTPAGlu) or its gadolinium complex, (C18DTPAGlu(Gd)), contains the same C18 hydrophobic moiety bound, through a lysine residue, to the DTPAGlu chelating agent. The mixed aggregates as well as the pure C18DTPAGlu aggregate, in the presence and absence of Gd, have been fully characterized by surface tension measurements, FT-PGSE-NMR, fluorescence quenching, and small-angle neutron scattering measurements. The structural characterization of the mixed aggregates C18DTPAGlu(Gd)-C18CCK8 indicates a spherical arrangement of the micelles with an external shell of approximately 21 A and an inner core of approximately 20 A. Both the DTPAGlu(Gd) complexes and the CCK8 peptides point toward the external surface. The measured values for relaxivity in saline medium at 20 MHz proton Larmor frequency and 25 degrees C are 18.7 mM(-)(1) s(-)(1). These values show a large enhancement in comparison with the isolated DTPAGlu(Gd) complex.

Peptide containing Vesicles as Selective Nanocarriers for Therapeutics and Diagnostics

Characterization of Multicomponent Aggregate Containing a Bioactive Peptide and a Gd Complex

Journal of Peptide Science, 2014

Nanotechnology is an expanding area of study with potentially pivotal applications in a disciplin... more Nanotechnology is an expanding area of study with potentially pivotal applications in a discipline as medicine where new biomedical active molecules or strategies are continuously developing. One of the principal drawbacks for the application of new therapies is the difficulty to cross membranes that represent the main physiological barrier in our body and in all living cells. Membranes are selectively permeable and allow the selective internalization of substances; generally, they form a highly impermeable barrier to most polar and charged molecules, and represent an obstacle for drug delivery, limiting absorption to specific routes and mechanisms. Viruses provide attracting suggestions for the development of targeted drug carriers as they have evolved naturally to deliver their genomes to host cells with high fidelity.

Activation of monocytic cells by immunostimulatory lipids conjugated to peptide antigens

Molecular BioSystems, 2012

Bacterial derived lipoproteins constitute potent macrophage activators in vivo and are effective ... more Bacterial derived lipoproteins constitute potent macrophage activators in vivo and are effective stimuli, enhancing the immune response especially with respect to low or non-immunogenic compounds. In the present study we have prepared branched lipopeptide constructs in which different (B- and T-cell) epitopes of Herpes simplex virus type 1, derived from glycoproteins B (gB) and D (gD), are linked to a synthetic lipid core. The ability of the lipid core peptide (LCP) constructs (LCP-gB and LCP-gD) to induce cytokine expression and activate the mitogen-activated protein kinase cascade has been evaluated and compared with the behaviour of the isolated epitopes and the lipid core. In this respect, the use of LCP technology coupled with the use of three different gB or gD peptide epitopes in the same branched constructs could represent an interesting approach in order to obtain efficient delivery systems in the development of a synthetic multiepitopic vaccine for the prevention of viral infections.

Conformational Modifications of gB from Herpes Simplex Virus Type 1 Analyzed by Synthetic Peptides

Journal of Medicinal Chemistry, 2013

Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformatio... more Entry of enveloped viruses requires fusion of viral and cellular membranes, driven by conformational changes of viral glycoproteins. The crystallized trimeric glycoprotein gB of herpes simplex virus has been described as a postfusion conformation, and several studies prove that like other class III fusion proteins, gB undergoes a pH-dependent switch between the pre- and postfusion conformations. Using several biophysical techniques, we show that peptides corresponding to the long helix of the gB postfusion structure interfere with the membrane fusion event, likely hampering the conformational rearrangements from the pre- to the postfusion structures. Those peptides represent good candidates for further design of peptidomimetic antagonists capable of blocking the fusion process.

Silver Nanoparticles as Potential Antibacterial Agents

Molecules (Basel, Switzerland)

Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widesp... more Multi-drug resistance is a growing problem in the treatment of infectious diseases and the widespread use of broad-spectrum antibiotics has produced antibiotic resistance for many human bacterial pathogens. Advances in nanotechnology have opened new horizons in nanomedicine, allowing the synthesis of nanoparticles that can be assembled into complex architectures. Novel studies and technologies are devoted to understanding the mechanisms of disease for the design of new drugs, but unfortunately infectious diseases continue to be a major health burden worldwide. Since ancient times, silver was known for its anti-bacterial effects and for centuries it has been used for prevention and control of disparate infections. Currently nanotechnology and nanomaterials are fully integrated in common applications and objects that we use every day. In addition, the silver nanoparticles are attracting much interest because of their potent antibacterial activity. Many studies have also shown an impor...

Journal of peptide science : an official publication of the European Peptide Society, 2014

In the last few years, research activity focused on peptide-based materials has been experiencing... more In the last few years, research activity focused on peptide-based materials has been experiencing an explosion of interest and a remarkable advancement of knowledge both on the fundamental side, i.e. the molecular mechanisms and forces that determine the growth of nanometric and mesoscopic structures (nanowires, nanotubes, self-assembled monolayers, fibers, and fibrils) from basic peptide motifs, and the applicative side, i.e. peptide-based compounds for electronics, biosensing, peptideassisted drug delivery, tissue engineering, and cell adhesion.