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Battistini L.,University of Parma | Burreddu P.,CNR Institute of Biomolecular Chemistry | Sartori A.,University of Parma | Arosio D.,CNR Institute of Molecular Science and Technologies | And 10 more authors.
Molecular Pharmaceutics | Year: 2014

Novel liposemipeptides hanging cyclic azabicycloalkane-RGD or aminoproline-RGD terminals were synthesized and incorporated into liposomal nanoparticles cAba/cAmpRGD-LNP5 3C/3D. Liposomes with similar composition and lacking semipeptide conjugates were constructed for comparison (LNP, 3A), and physical encapsulation of the anticancer doxorubicin drug in both targeted and untargeted liposomes was accomplished. Microstructural analysis performed by dynamic light scattering (DLS), small-angle neutron scattering (SANS), and electron paramagnetic resonance (EPR) revealed that the conjugated nanoparticles presented an average size of 80 nm and were constituted by 5 nm thick unilamellar liposome bilayer. Flow cytometry and fluorescent microscopy studies showed that 3C-DOXO and 3D-DOXO efficiently delivered the drug into the nuclei of both quiescent and proliferating cells even in a high serum concentration environment. The uptake of doxorubicin when carried by liposomes was faster than that of the free drug, and 30 min incubation was sufficient to load cell nuclei with doxorubicin. Targeted liposomes significantly induced cell death of human breast adenocarcinoma MCF7 cells (IC50 = 144 nM, 3C-DOXO; IC 50 = 274 nM, 3D-DOXO), about 2- to 6-fold more potent than free doxorubicin or 3A-DOXO controls (IC50 = 527 and 854 nM, respectively). These results suggest that cAba/cAmpRGD liposomal nanoparticles hold promise for the rapid and efficient delivery of chemotherapeutic agents to αVβ3-expressing tumor cells. © 2014 American Chemical Society.


Della Vecchia N.F.,University of Naples Federico II | Luchini A.,University of Naples Federico II | Napolitano A.,University of Naples Federico II | Derrico G.,University of Naples Federico II | And 7 more authors.
Langmuir | Year: 2014

Despite the growing technological interest of polydopamine (dopamine melanin)-based coatings for a broad variety of applications, the factors governing particle size, shape, and electronic properties of this bioinspired multifunctional material have remained little understood. Herein, we report a detailed characterization of polydopamine growth, particle morphology, and paramagnetic properties as a function of dopamine concentration and nature of the buffer (pH 8.5). Dynamic Light Scattering data revealed an increase in the hydrodynamic radii (Rh) of melanin particles with increasing dopamine concentration in all buffers examined, especially in phosphate buffer. Conversely, a marked inhibition of particle growth was apparent in Tris buffer, with Rh remaining as low as <100 nm during polymerization of 0.5 mM dopamine. Small angle neutron scattering data suggested formation of bidimensional structures in phosphate or bicarbonate buffers, while apparently three-dimensional fractal objects prevailed in Tris buffer. Finally, electron paramagnetic resonance spectra revealed a broader signal amplitude with a peculiar power saturation decay profile for polydopamine samples prepared in Tris buffer, denoting more homogeneous paramagnetic centers with respect to similar samples obtained in phosphate and bicarbonate buffers. Overall, these results disclose Tris buffer as an efficient modulator of polydopamine buildup and properties for the rational control and fine-tuning of melanin aggregate size, morphology, and free radical behavior. © 2014 American Chemical Society.


Emendato A.,University of Naples Federico II | Spadaccini R.,University of Naples Federico II | Spadaccini R.,University of Sannio | De Santis A.,University of Naples Federico II | And 5 more authors.
FEBS Letters | Year: 2016

Many age-related neurodegenerative diseases, including Alzheimer Disease (AD), are elicited by an interplay of genetic, environmental, and dietary factors. Food rich in Omega-3 phospholipids seems to reduce the AD incidence. To investigate the molecular basis of this beneficial effect, we have investigated by CD and ESR studies the interaction between the Alzheimer peptide Aβ-(1-42) and biomimetic lipid bilayers. The inclusion of 1,2-didocosahexaenoyl-sn-glycero-3-phosphocholine does not change significantly the bilayers organization, but favors its Aβ-(1-42) interaction. The Omega-3 lipid amount modulates the effect intensity, suggesting a peptide selectivity for membranes containing polyunsatured fatty acids (PUFA) and providing hints for the mechanism and therapy of AD. © 2016 Federation of European Biochemical Societies.


D'Errico G.,University of Naples Federico II | D'Errico G.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase | Ercole C.,University of Naples Federico II | Lista M.,University of Naples Federico II | And 7 more authors.
Biochimica et Biophysica Acta - Biomembranes | Year: 2011

Binding to cell membrane, followed by translocation into the cytosol and RNA degradation, is a necessary requirement to convert a ribonuclease into a cytotoxin for malignant tumor cells. In this paper, we investigate the membrane binding attitude of bovine seminal ribonuclease (BS-RNase) and its variant G38K-BS-RNase, bearing an enforced cluster of positive charges at the N-termini surface. By using a combination of biophysical techniques, including CD, SPR and ESR, we find for the two proteins a common, two-step mechanism of interaction with synthetic liposomes, an initial binding to the bilayer surface, driven by electrostatic interactions, followed by a shallow penetration in the lipid core. Protein binding effectively perturbs lipid packing and dynamics. Remarkably, the higher G38K-BS-RNase membrane interacting capability well correlates with its increased cytotoxicity for tumor cells. Overall, these studies shed light on the mechanism of membrane binding and perturbation, proving definitely the importance of electrostatic interactions in the cytotoxic activity of BS-RNase, and provide a rational basis to design proteins with anticancer potential. © 2011 Elsevier B.V.


Montesarchio D.,University of Naples Federico II | Mangiapia G.,University of Naples Federico II | Mangiapia G.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase | Vitiello G.,University of Naples Federico II | And 8 more authors.
Dalton Transactions | Year: 2013

In continuation with our studies concerning the synthesis, characterization and biological evaluation of nucleolipidic Ru(iii) complexes, a novel design for this family of potential anticancer agents is presented here. As a model compound, a new uridine-based nucleolipid has been prepared, named HoUrRu, following a simple and versatile synthetic procedure, and converted into a Ru(iii) salt. Stable formulations of this highly functionalized Ru(iii) complex have been obtained by co-aggregation with either the zwitterionic lipid POPC or the cationic DOTAP, which have been subjected to an in-depth microstructural characterization, including DLS, SANS and EPR measurements. The in vitro bioactivity profile of HoUrRu, as a pure compound or in formulation with POPC or DOTAP, reveals high antiproliferative activity against MCF-7 and WiDr human cancer cell lines. © 2013 The Royal Society of Chemistry.


Vitiello G.,University of Naples Federico II | Vitiello G.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase | Falanga A.,University of Naples Federico II | Falanga A.,CNR Institute of Biostructure and Bioimaging | And 7 more authors.
Biochimica et Biophysica Acta - Biomembranes | Year: 2011

Lipid membranes play a key role in the viral life cycle. Enveloped viruses particularly require a sequence of fusion and fission events between the viral envelope and the target membranes for entry into the cell and egress from it. These processes are controlled by one or more viral glycoproteins that undergo conformational changes favoring the necessary micro- and mesoscopic lipid re-arrangements. Multiple regions from these glycoproteins are thought to interact with the membranes, according to a concerted mechanism, in order to generate the distortion necessary for fusion. In this work, we perform an EPR study on the role played by the membrane composition in tuning the interaction between lipid bilayers and two peptides, gH626-644 and gB632-650, that are highly fusogenic fragments of the gH and gB glycoproteins of herpes simplex virus. Our results show that both peptides interact with lipid bilayers, perturbing the local lipid packing. gH626-644 localizes close to the hydrophilic bilayer surface, while gB632-650 penetrates deeply into the membrane. Chain perturbation by the peptides increases in the presence of charged phospholipids. Finally, cholesterol does not alter the ability of gB632-650 to penetrate deeply in the membrane, whereas it limits penetration of the gH626-644 peptide to the more external layer. The different modes of interaction result in a higher fusogenic ability of gB632-650 towards cholesterol-enriched membranes, as demonstrated by lipid mixing assays. These results suggest that the mechanism of action of the gH and gB glycoproteins is modulated by the properties and composition of the phospholipid bilayer. © 2011 Elsevier B.V. All rights reserved.


Luchini A.,University of Naples Federico II | Luchini A.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase | Heenan R.K.,Rutherford Appleton Laboratory | Paduano L.,University of Naples Federico II | And 3 more authors.
Physical Chemistry Chemical Physics | Year: 2016

SuperParamagnetic Iron Oxide Nanoparticles (SPIONs) represent a suitable system for several applications especially in nanomedicine. Great efforts have been made to design stable and biocompatible functionalized SPIONs suitable for diagnostics and drug delivery. In particular, zwitterionic-surfactant functionalized SPIONs, obtained through a coating strategy based on hydrophobic interaction, are promising systems for biomedical applications. The size of functionalized SPIONs has emerged as a crucial parameter determining their fate in living organisms. However, not all the proposed functionalization strategies lead to monodispersed systems and SPION clustering often occurs. In this study, we report a systematic investigation on different surfactant-functionalized SPIONs in order to explore the possibility of tuning the particle size by choosing an appropriate amphiphilic molecule. By combining Small-Angle Neutron Scattering (SANS) and Dynamic Light Scattering (DLS) analysis, we have provided a detailed description of the functionalized SPION structure. Furthermore, we have also related the surfactant aggregation properties, i.e. the Critical Micelle Concentration (CMC), to their efficiency in coating the SPION surface. A lack in the formation of a compact shell leads to a clusters formation. On this basis, the present study contributes to furnishing decisive information to define synthetic strategies able to tune functionalized-SPION design. © the Owner Societies 2016.


Simeone L.,University of Naples Federico II | Mangiapia G.,University of Naples Federico II | Mangiapia G.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase | Irace C.,University of Naples Federico II | And 8 more authors.
Molecular BioSystems | Year: 2011

Novel thymidine- or uridine-based nucleolipids, containing one hydrophilic oligo(ethylene glycol) chain and one or two oleic acid residues (called ToThy, HoThy and DoHu), have been synthesized with the aim to develop bio-compatible nanocarriers for drug delivery and/or produce pro-drugs. Microstructural characterization of their aggregates has been determined in pure water and in pseudo-physiological conditions through DLS and SANS experiments. In all cases stable vesicles, with mean hydrodynamic radii ranging between 120 nm and 250 nm have been revealed. Biological validation of the nucleolipidic nanocarriers was ensured by evaluation of their toxicological profiles, performed by administration of the nanoaggregates to a panel of different cell lines. ToThy exhibited a weak cytotoxicity and, at high concentration, some ability to interfere with cell viability and/or proliferation. In contrast, DoHu and HoThy exhibited no toxicological relevance, behaving similarly to POPC-based liposomes, widely used for systemic drug delivery. Taken together, these results show nucleolipid-based nanocarriers as finely tunable, multi-functional self-assembling materials of interest for the in vivo transport of biomolecules or drugs. © The Royal Society of Chemistry.


Giustini M.,University of Rome La Sapienza | Giustini M.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase | Autullo M.,University of Rome La Sapienza | Mennuni M.,University of Rome La Sapienza | And 2 more authors.
Sensors and Actuators, B: Chemical | Year: 2012

The design and characterization of an optical biosensor based on a photosynthetic protein deposited on a quartz surface is here presented. The protein reaction center (RC), purified from Rhodobacter sphaeroides, has been immobilized in alternate layers with the cationic polymer poly(dimethyl diallyl) ammonium chloride (PDDA). In this assembly the protein retains its integrity and functionality maintaining its ability to bind herbicides. Upon exposure to continuous light some RC absorbance bands dramatically reduce their intensity (bleaching) and the extent of such a bleaching reflects the amount of bound herbicides. These properties have been exploited for the design of a simple optical biosensor for herbicide. The characterization of the biosensor in detecting the broad family of triazine herbicides is presented. Performance characteristics, such as limits of detection (LOD) and quantification (LOQ), upper determination limit (UDL) and linear range for each herbicide were determined. Among the most striking features of the biosensor are the long lifetime (several months), the high reproducibility and the relatively high sensitivity of detection that can be further enhanced by preconcentrating the samples to be analysed. As a whole, these characteristics coupled to the low demanding instrumental setup, let the RC/PDDA assembly particularly appealing even for the realization of a stand alone analytical apparatus. © 2012 Elsevier B.V. All rights reserved.


Avino P.,DIT | Manigrasso M.,DIT | Cuomo F.,Consorzio Interuniversitario per Lo Sviluppo Dei Sistemi ande Interfase
RSC Advances | Year: 2015

This work describes a methodological approach based on natural radioactivity measurements aimed at interpreting air pollution episodes in urban air. The use of such parameters helps in the understanding of the temporal behaviors of seasonal primary (benzene and carbon monoxide) and secondary (nitrogen dioxide and ozone) pollutants. A comparison between the daily concentrations of primary and secondary pollutants and the natural radioactivity trends, considered as an index of the dynamic of the low atmospheric boundary layers, evidences that acute episodes of air pollution in downtown Rome occur in wintertime due to high atmospheric stability (primary pollution) and in summertime because of the strong diurnal atmospheric mixing (secondary pollution). © The Royal Society of Chemistry 2015.

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