Daniela Iannazzo

Hybrid composites made of multiwalled carbon nanotubes functionalized with Fe3O4 nanoparticles for tissue engineering applications

A straightforward technique for functionalization of multiwalled carbon nanotubes (MWCNTs) with magnetite (Fe(3)O(4)) nanoparticles was developed. Iron oxide nanoparticles were deposited on MWCNT surfaces by a deposition-precipitation method using Fe(3+)/Fe(2+) salts precursors in basic solution. The characterizations by HRTEM, XRD, SEM/EDX, AAS and TPR analyses confirmed the successful formation of magnetic iron oxide nanoparticles on the MWCNT surface. Fe(3)O(4)/MWCNT hybrid composites were analysed in vitro by incubation with mesenchymal stem cells for 1, 3 and 7 days, either in the presence or absence of a static magnetic field. Analysis of cell proliferation was performed by the MTT assay, quantification of cellular stress was performed by the Lactate Dehydrogenase assay and analysis of cell morphology was performed by actin immunofluorescence and scanning electron microscopy. Results demonstrate that the introduction of magnetite into the MWCNT structure increases biocompatibility of oxidized MWCNTs. In addition, the presence of a static magnetic field further increases Fe(3)O(4)/MWCNT influence on cell behaviour. These results demonstrate this novel Fe(3)O(4)/MWCNT hybrid composite has good potential for tissue engineering applications.

Synthesis and Biological Activity of Phosphonated Nucleosides: Part 1Furanose, Carbocyclic and Heterocyclic Analogues

Phosphonated nucleosides represent a promising alternative in the improvement of the biological activity of nucleoside analogues in antiviral and anticancer chemotherapy. The basic concept, the chemistry, the different structural modifications and their effects on the antiviral potency will be discussed in this review.

Recent Advances in Carbon Nanotubes as Delivery Systems for Anticancer Drugs

Problems associated with the administration of anticancer drugs, such as limited solubility, poor biodistribution,lack of selectivity, and healthy tissue damage, can be overcome by the implementation of drug delivery systems. A wide range of materials, including liposomes, microspheres, polymers and recently, carbon nanotubes (CNTs), have been investigated for delivering anticancer drugs on the purpose of reducing the number of necessary administrations, providing more localized and better use of the active agents, and increasing patient compliance. Carbon nanotubes (CNTs) have attracted particular attention as carriers of biologically relevant molecules due to their unique physical, chemical and physiological properties. The exact relationship between the physical-chemical properties of carbon nanotubes, their cell to-cell interactions, reactivity, and biological/systemic consequences are relevant issues and it is important to know suchinter-relationships beforehand to employ the benefits of these nanomaterials without the hazardous consequences. The purpose of this review is to present highlight of recent developments in the application of carbon nanotubes as cargoes for anti cancer drugs and in the diagnosis of cancer diseases.

Experimental and theoretical study of the 1,3-dipolar cycloaddition between d-glyceraldehyde nitrones and acrylates. Diastereoselective approach to 4-hydroxy pyroglutamic acid derivatives

Abstract The 1,3-dipolar cycloaddition reactions of five d -glyceraldehyde nitrones with alkyl acrylates and Oppolzers sultam acrylamide have been studied in detail, the study including double chiral induction experiments. A complete theoretical study of the reaction has also been carried out using density functional methods (B3LYP/6-31G*) in which both ortho and meta channels leading to 3,5- and 3,4-disubstituted isoxazolidines, respectively, were considered. The adducts obtained from the cycloaddition reactions have been further used for the stereoselective synthesis of protected 4-hydroxy pyroglutamic acids, particularly the (2S,4S)-isomer, which is prepared from the major adducts of the cycloaddition reactions.

Antiviral activity of seed extract from Citrus bergamia towards human retroviruses

The effects of an extract from Citrus bergamia (BSext) and those of two products purified from the same extract, that is, nomilin and limonin, and reference compounds, towards HTLV-1 have been reported. Moreover, they were also compared with those obtained towards HIV-1. Results showed that the efficacy of both BSext and limonin in inhibiting HTLV-1 as well as HIV-1 expression in infected cells, as evaluated by comparable quantitative assays, was close to that of the effective, reference compounds, respectively. The protective effect of BSext and of the purified products was associated with the inhibition of both HTLV-1 and HIV-1 RT activities in conceptually similar, cell-free assays. The cytotoxicity of the assayed compounds of natural origin was substantially less pronounced than that of the reference compounds, thus showing a favourable selectivity index for the novel BSext product.

C-Alkoxycarbonyl Nitrones: Building Blocks for the Synthesis of Butenolides, Lactams and Modified Nucleosides

Abstract: Elaboration of isoxazolidines derived from the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to suitably substituted alkenes leads to the development of new synthetic methodologies for the preparation of a wide range of natural products and derivatives including lactones, lactams and complex nucleosides. The insertion of a chiral centre in position α, with respect to nitrone functionality, or the presence of a chiral auxiliary at the nitrogen atom have allowed the enantioselective synthesis of the same compounds.

Diastereo- and enantioselective synthesis of N,O-nucleosides

Abstract The diastereo- and enantioselective synthesis of α- and β-3′-hydroxymethyl-N,O-nucleosides is described, based on the 1,3-dipolar cycloaddition of a N-glycosyl nitrone. Two approaches have been evaluated: the one-step procedure, which uses vinyl nucleobases, showed a better stereoselectivity towards β-nucleosides.

Toxicological assessment of multi-walled carbon nanotubes on A549 human lung epithelial cells

An in vitro model resembling the respiratory epithelium was used to investigate the biological response to laboratory-made pristine and functionalised multi-walled carbon nanotubes (pMWCNT and MWCNT-COOH). Cell uptake was analysed by MWCNT-COOH, FITC labelled and the effect of internalisation was evaluated on the endocytic apparatus, mitochondrial compartment and DNA integrity. In the dose range 12.5-100μgml(-1), cytotoxicity and ROS generation were assayed, evaluating the role of iron (the catalyst used in MWCNTs synthesis). We observed a correlation between MWCNTs uptake and lysosomal dysfunction and an inverse relationship between these two parameters and cell viability (P<0.01). In particular, pristine-MWCNT caused a time- and dose-dependent ROS increase and higher levels of lipid hydroperoxides compared to the controls. Mitochondrial impairment was observed. Conversely to the functionalised MWCNT, higher micronuclei (MNi) frequency was detected in mono- and binucleate pMWCNT-treated cells, underlining an aneugenic effect due to mechanical damage. Based on the physical and chemical features of MWCNTs, several toxicological pathways could be activated in respiratory epithelium upon their inhalation. The biological impacts of nano-needles were imputable to their efficient and very fast uptake and to the resulting mechanical damages in cell compartments. Lysosomal dysfunction was able to trigger further toxic effects.

A Stereoselective Approach to Isoxazolidinyl Nucleosides

A stereoselective approach towards isoxazolidinyl nucleosides has been designed. The 1,3-dipolar cycloaddition of a C-chiral nitrone with purine and pyrimidine nucleobases produces thymidine and adenine N,O-nucleosides, in enantiomerically pure forms.

graphene quantum dots for cancer targeted drug delivery

A biocompatible and cell traceable drug delivery system Graphene Quantum Dots (GQD) based, for the targeted delivery of the DNA intercalating drug doxorubicin (DOX) to cancer cells, is here reported. Highly dispersible and water soluble GQD, synthesized by acidic oxidation and exfoliation of multi-walled carbon nanotubes (MWCNT), were covalently linked to the tumor targeting module biotin (BTN), able to efficiently recognize biotin receptors over-expressed on cancer cells and loaded with DOX. Biological test performed on A549 cells reported a very low toxicity of the synthesized carrier (GQD and GQD-BTN). In GQD-BTN-DOX treated cancer cells, the cytotoxicity was strongly dependent from cell uptake which was greater and delayed after treatment with GQD-BTN-DOX system with respect to what observed for cells treated with the same system lacking of the targeting module BTN (GQD-DOX) or with the free drug alone. A delayed nuclear internalization of the drug is reported, due to the drug detachment from the nanosystem, triggered by the acidic environment of cancer cells.