Mazzaglia A.,CNR Institute of Nanostructured Materials |
Bondi M.L.,CNR Institute of Nanostructured Materials |
Scala A.,CNR Institute of Nanostructured Materials |
Zito F.,CNR Institute of Biomedicine and Molecular Immunology Alberto Monroy |
And 10 more authors.
Biomacromolecules | Year: 2013
Amphiphilic cyclodextrin (ACyD) provides water-soluble and adaptable nanovectors by modulating the balance between the hydrophobic and hydrophilic chains at both CyD sides. This work aimed to design nanoassemblies based on nonionic and hydrophilic ACyD (SC6OH) for the delivery of a poor-water-soluble organotin(IV)-porphyrin derivative [(Bu3Sn)4TPPS] to melanoma cancer cells. To characterize the porphyrin derivatives under simulated physiological conditions, a speciation was performed using complementary techniques. In aqueous solution (≤20 μM), (Bu3Sn) 4TPPS primarily exists as a monomer (2 in Figure 1), as suggested by the low static anisotropy (ρ ≈ 0.02) with a negligible formation of porphyrin supramolecular aggregates. MALDI-TOF spectra indicate the presence of moieties (i.e., [(Bu3Sn)3TPPS]-) that are derivatives of the monomeric species. Spectrofluorimetry coupled with potentiometric measurements primarily assesses the presence of the hydrolytic [(Bu3Sn)4TPPS (OH)4]4- species under physiological conditions. Nanoassemblies of (Bu3Sn) 4TPPS/SC6OH were prepared by dispersion of organic films in PBS at pH 7.4 and were investigated using a combination of spectroscopic and morphological techniques. The UV-vis and emission fluorescence spectra of the (Bu3Sn)4TPPS/SC6OH reveal shifts in the peculiar bands of the organotin(IV)-porphyrin derivative due to its interaction with the ACyD supramolecular assemblies in aqueous solution. The mean size was within the range of 100-120 nm. The ξ-potential was negative (-16 mV) for the (Bu 3Sn)4TPPS/SC6OH nanoassemblies, with an entrapment efficiency of approximately 67%. The intracellular delivery, cytotoxicity, nuclear morphology and cell growth kinetics were evaluated via fluorescence microscopy on A375 human melanoma cells. The delivery of (Bu3Sn) 4TPPS by ACyD with respect to free (Bu3Sn)4TPPS increases the internalization efficiency and cytotoxicity to induce apoptotic cell death and, at lower concentrations, changes the cellular morphology and prevents cell proliferation. © 2013 American Chemical Society.
Notomista E.,University of Naples Federico II |
Falanga A.,CNR Institute of Neuroscience |
Fusco S.,University of Naples Federico II |
Pirone L.,CNR Institute of Neuroscience |
And 7 more authors.
Microbial Cell Factories | Year: 2015
Background: Pathogenic bacteria easily develop resistance to c onventional antibiotics so that even relatively new molecules are quickly losing efficacy. This strongly encourages the quest of new antimicrobials especially for the treatment of chronic infections. Cationic antimicrobial peptides (CAMPs) are small positively charged peptides with an amphipathic structure, active against Gram-positive and Gram-negative bacteria, fungi, as well as protozoa. Results: A novel (CAMP)-like peptide (VLL-28) was identified in the primary structure of a transcription factor, Stf76, encoded by pSSVx, a hybrid plasmid-virus from the archaeon Sulfolobus islandicus. VLL-28 displays chemical, physical and functional properties typical of CAMPs. Indeed, it has a broad-spectrum antibacterial activity and acquires a defined structure in the presence of membrane mimetics. Furthermore, it exhibits selective leakage and fusogenic capability on vesicles with a lipid composition similar to that of bacterial membranes. VLL-28 localizes not only on the cell membrane but also in the cytoplasm of Escherichia coli and retains the ability to bind nucleic acids. These findings suggest that this CAMP-like peptide could exert its antimicrobial activity both on membrane and intra cellular targets. Conclusions: VLL-28 is the first CAMP-like peptide identified in the archaeal kingdom, thus pointing to archaeal microorganisms as cell factories to produce antimicrobial molecules of biotechnological interest. Furthermore, results from this work show that DNA/RNA-binding proteins could be used as sources of CAMPs. © 2015 Notomista et al.
Bisceglie F.,University of Parma |
Bisceglie F.,Circmsb Consorzio Interuniversitario Of Ricerca In Chimica Dei Metalli Nei Sistemi Biologici |
Pinelli S.,University of Parma |
Pinelli S.,Circmsb Consorzio Interuniversitario Of Ricerca In Chimica Dei Metalli Nei Sistemi Biologici |
And 9 more authors.
Journal of Inorganic Biochemistry | Year: 2012
To improve the solubility in aqueous media of bis(citronellalthiosemicarbazonato)copper(II) [Cu(S-tcitr)2], a compound that is effective in inhibiting cell growth of U937 cell line, the ligand was modified adding an ethylmorpholine group. [Cu(S-tcitr)2] and [Cu(Etmorph-S-tcitr)2] cytotoxic effects are compared using as a model U937 cells. [Cu(Etmorph-S-tcitr)2] results more effective in cell growth inhibition (IC50: 2.3 vs 14.8 μM). Apoptosis in [Cu(Etmorph-S-tcitr)2] treated cells was apparent after 8 h, with increased caspase activities, and these effects were not observed for [Cu(S-tcitr)2]. During the exposure to [Cu(Etmorph-S-tcitr) 2], ROS (reactive oxygen species) and TBARS (Thiobarbituric acid reactive substances) significantly increased, coupled with reduced glutathione (GSH) levels and significant activation of superoxide dismutase (SOD). These intracellular scavengers seem to limit the early ROS and TBARS increases in U937 cells exposed to [Cu(S-tcitr)2]. Both complexes interacted in vitro with naked DNA: UV-visible and CD titration reveal that they can induce DNA structure modifications in a distinct way. Furthermore, the complexes induced DNA damage on U937 cells at concentrations higher than IC50. The mechanisms of action and the effects of these two complexes are remarkably different even though they have the same coordination geometry around copper(II) and differ only for the presence of the ethylmorpholine group. © 2012 Elsevier Inc. All rights reserved.
Mercurio F.A.,National Research Council Italy |
Di Natale C.,University of Naples Federico II |
Di Natale C.,Center for Advanced Biomaterials for Health Care |
Pirone L.,Circmsb Consorzio Interuniversitario Of Ricerca In Chimica Dei Metalli Nei Sistemi Biologici |
And 12 more authors.
ChemBioChem | Year: 2015
Odin is a protein belonging to the ANKS family, and has two tandem Sam domains. The first, Odin-Sam1, binds to the Sam domain of the EphA2 receptor (EphA2-Sam); this interaction could be crucial for the regulation of receptor endocytosis and might have an impact on cancer. Odin-Sam1 associates with EphA2-Sam by adopting a "mid-loop/end-helix" model. In this study three peptide sequences, encompassing the mid-loop interacting portion of Odin-Sam1 and its C-terminal α5 helix, were designed. Their conformational properties were analyzed by CD and NMR. In addition, their abilities to interact with EphA2-Sam were investigated by SPR studies. The peptides adopt a predominantly disordered state in aqueous buffer, but a higher helical content is evident in the presence of the cosolvent trifluoroethanol. Dissociation constants towards EphA2-Sam were in the high micromolar range. The structural findings suggest further routes for the design of potential anti-cancer therapeutics as inhibitors of EphA2-Sam heterotypic interactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.