Silvia Nappini

Magnetoliposomes for controlled drug release in the presence of low-frequency magnetic field

In this work we have studied the effect of a low-frequency alternating magnetic field (LF-AMF) on the permeability of magnetoliposomes, i.e. liposomes including magnetic nanoparticles within their water pool. Large unilamellar liposomes loaded with magnetic cobalt ferrite nanoparticles (CoFe2O4) have been prepared and characterized. Structural characterization of the liposomal dispersion has been performed by dynamic light scattering (DLS). The enhancement of liposome permeability upon exposure to LF-AMF has been measured as the self-quenching decrease of a fluorescent hydrophilic molecule (carboxyfluorescein, CF) entrapped in the liposome pool. Liposome leakage has been monitored as a function of field frequency, time of exposure and concentration, charge and size of the embedded nanoparticles. The results show that CF release from magnetoliposomes is strongly promoted by LF-AMF, reasonably as a consequence of nanoparticle motions in the liposome pool at the applied frequency. CF release as a function of time in magnetoliposomes unexposed to magnetic field follows Fickian diffusion, while samples exposed to LF-AMF show zero-order kinetics, consistently with an anomalous transport, due to an alteration of the bilayer permeability. These preliminary results open up new perspectives in the use of these systems as carriers in targeted and controlled release of drugs.

Structure and permeability of magnetoliposomes loaded with hydrophobic magnetic nanoparticles in the presence of a low frequency magnetic field

In this paper we describe the effect of a low frequency alternating magnetic field (LF-AMF) on the structure and permeability of magnetoliposomes, i.e. liposomes formulated in the presence of magnetic nanoparticles. Hydrophobic cobalt ferrite nanoparticles (CoFe2O4) coated with a shell of oleic acid were prepared, characterized and employed in the preparation of magnetoliposomes. The stability of the lipid bilayer after the application of an oscillating magnetic field was studied by means of Dynamic Light Scattering (DLS), Small Angle Scattering of X-rays (SAXS) and Differential Scanning Calorimetry (DSC). The enhancement of liposome permeability upon LF-AMF exposure was measured as the self-quenching decrease of the fluorescent molecule carboxyfluorescein (CF) entrapped in the liposome pool. Carboxyfluorescein leakage from magnetoliposomes was investigated as a function of field frequency, time of exposure to the magnetic field, and cobalt ferrite nanoparticles concentration. Kinetics of CF release from LF-AMF treated magnetoliposomes, monitored through the fluorescence intensity increase during time, highlights a slow release of CF during the first hours, followed by a faster release a few hours after the field treatment which leads to a complete leakage of CF. DSC provides insights about the effect of the LF-AMF treatment, showing that the first few hours correspond to a complete loss of the transition peak from the lamellar gel (Lβ) phase to the liquid crystalline (Lα) phase of the PC bilayers. These results suggest that the slow release takes place through the formation of local pores or defects at the membrane level, while the fast release corresponds to an increased permeability of the membrane that can be related to a structural change of the bilayer.

Fast One-Pot Synthesis of MoS2/Crumpled Graphene p–n Nanonjunctions for Enhanced Photoelectrochemical Hydrogen Production

Aerosol processing enables the preparation of hierarchical graphene nanocomposites with special crumpled morphology in high yield and in a short time. Using modular insertion of suitable precursors in the starting solution, it is possible to synthesize different types of graphene-based materials ranging from heteroatom-doped graphene nanoballs to hierarchical nanohybrids made up by nitrogen-doped crumpled graphene nanosacks that wrap finely dispersed MoS2 nanoparticles. These materials are carefully investigated by microscopic (SEM, standard and HR TEM), diffraction (grazing incidence X-ray diffraction (GIXRD)) and spectroscopic (high resolution photoemission, Raman and UV-visible spectroscopy) techniques, evidencing that nitrogen dopants provide anchoring sites for MoS2 nanoparticles, whereas crumpling of graphene sheets drastically limits aggregation. The activity of these materials is tested toward the photoelectrochemical production of hydrogen, obtaining that N-doped graphene/MoS2 nanohybrids are seven times more efficient with respect to single MoS2 because of the formation of local p-n MoS2/N-doped graphene nanojunctions, which allow an efficient charge carrier separation.

Understanding the Oxygen Evolution Reaction Mechanism on CoOx using Operando Ambient-Pressure X-ray Photoelectron Spectroscopy

Photoelectrochemical water splitting is a promising approach for renewable production of hydrogen from solar energy and requires interfacing advanced water-splitting catalysts with semiconductors. Understanding the mechanism of function of such electrocatalysts at the atomic scale and under realistic working conditions is a challenging, yet important, task for advancing efficient and stable function. This is particularly true for the case of oxygen evolution catalysts and, here, we study a highly active Co3O4/Co(OH)2 biphasic electrocatalyst on Si by means of operando ambient-pressure X-ray photoelectron spectroscopy performed at the solid/liquid electrified interface. Spectral simulation and multiplet fitting reveal that the catalyst undergoes chemical-structural transformations as a function of the applied anodic potential, with complete conversion of the Co(OH)2 and partial conversion of the spinel Co3O4 phases to CoO(OH) under precatalytic electrochemical conditions. Furthermore, we observe new spectral features in both Co 2p and O 1s core-level regions to emerge under oxygen evolution reaction conditions on CoO(OH). The operando photoelectron spectra support assignment of these newly observed features to highly active Co4+ centers under catalytic conditions. Comparison of these results to those from a pure phase spinel Co3O4 catalyst supports this interpretation and reveals that the presence of Co(OH)2 enhances catalytic activity by promoting transformations to CoO(OH). The direct investigation of electrified interfaces presented in this work can be extended to different materials under realistic catalytic conditions, thereby providing a powerful tool for mechanism discovery and an enabling capability for catalyst design.

Influence of TiO2 electronic structure and strong metal–support interaction on plasmonic Au photocatalytic oxidations

Aiming at understanding how plasmonic reactions depend on important parameters such as metal loading and strong metal–support interaction (SMSI), we report the plasmonic photodegradation of formic acid (FA) under green LED irradiation employing three TiO2 supports (stoichiometric TiO2, N-doped TiO2, black TiO2) modified with Au nanoparticles (NPs) 3–6 nm in size. The rate of FA photooxidation follows different trends depending on Au loading for stoichiometric and doped Au/TiO2 materials. In the first case, the only contribution of hot electron transfer produces a volcano-shaped curve of photoreaction rates with increasing Au loading. When TiO2 contains intra-bandgap states the photoactivity increases linearly with the amount of Au NPs due to the concomitant enhancement produced by hot electron transfer and plasmon resonant energy transfer (PRET). The role of PRET is supported by finite element method simulations, which show that the increase in both Au NP inter-distance and SMSI enhances the probability of charge carrier generation at the Au/TiO2 interface.

Thiol-ene mediated neoglycosylation of collagen patches: a preliminary study.

Despite the relevance of carbohydrates as cues in eliciting specific biological responses, the covalent surface modification of collagen-based matrices with small carbohydrate epitopes has been scarcely investigated. We report thereby the development of an efficient procedure for the chemoselective neoglycosylation of collagen matrices (patches) via a thiol-ene approach, between alkene-derived monosaccharides and the thiol-functionalized material surface. Synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), Fourier transform-infrared (FT-IR), and enzyme-linked lectin assay (ELLA) confirmed the effectiveness of the collagen neoglycosylation. Preliminary biological evaluation in osteoarthritic models is reported. The proposed methodology can be extended to any thiolated surface for the development of smart biomaterials for innovative approaches in regenerative medicine.

Glucose is a key driver for GLUT1-mediated nanoparticles internalization in breast cancer cells

The mesenchymal state in cancer is usually associated with poor prognosis due to the metastatic predisposition and the hyper-activated metabolism. Exploiting cell glucose metabolism we propose a new method to detect mesenchymal-like cancer cells. We demonstrate that the uptake of glucose-coated magnetic nanoparticles (MNPs) by mesenchymal-like cells remains constant when the glucose in the medium is increased from low (5.5 mM) to high (25 mM) concentration, while the MNPs uptake by epithelial-like cells is significantly reduced. These findings reveal that the glucose-shell of MNPs plays a major role in recognition of cells with high-metabolic activity. By selectively blocking the glucose transporter 1 channels we showed its involvement in the internalization process of glucose-coated MNPs. Our results suggest that glucose-coated MNPs can be used for metabolic-based assays aimed at detecting cancer cells and that can be used to selectively target cancer cells taking advantage, for instance, of the magnetic-thermotherapy.

Magnetic nanoparticle clusters as actuators of ssDNA release

One of the major areas of research in nanomedicine is the design of drug delivery systems with remotely controllable release of the drug. Despite the enormous progress in the field, this aspect still poses a challenge, especially in terms of selectivity and possible harmful interactions with biological components other than the target. We report an innovative approach for the controlled release of DNA, based on clusters of core-shell magnetic nanoparticles. The primary nanoparticles are functionalized with a single-stranded oligonucleotide, whose pairing with a half-complementary strand in solution induces clusterization. The application of a low frequency (6 KHz) alternating magnetic field induces DNA melting with the release of the single strand that induces clusterization. The possibility of steering and localizing the magnetic nanoparticles, and magnetically actuating the DNA release discloses new perspectives in the field of nucleic-acid based therapy.

Lysozyme interaction with negatively charged lipid bilayers: protein aggregation and membrane fusion

We report on the interaction of hen egg-white lysozyme (HEWL) with lipid vesicles in terms of surface-induced protein conformational variation and subsequent aggregation. In particular, we investigated the variations of the secondary structure of native lysozyme in the presence of liposomes with different surface charge density, resulting from different molar ratios of the zwitterionic POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and the negatively charged POPG (1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1′-rac-glycerol)). It is well known that the main driving force involved in the interaction between globally anionic liposomes and lysozyme is electrostatic compensation, which, in some cases, produces extended aggregation. Moreover the presence of membranes can induce unfolding in the protein. In order to understand the main determinants of such phenomena, we probed simultaneously lysozyme-induced vesicle fusion events, variations in the secondary structure of the protein and its effect on liposomal membrane fluidity. We found that above a charge-density threshold, the association with vesicles results in modifications of the native structure associated with a decrease of liposomal membrane fluidity. Electron microscopy images revealed that the above described interactions result in mesoscopic structural changes, i.e. liposome clustering and fusion, together with the appearance of elongated structures, reminiscent of fibrillar aggregates. Additionally, a confocal microscopy analysis revealed that upon interaction with giant unilamellar vesicles (GUVs) of the same lipid composition where the above interactions were observed, a prompt insertion of lysozyme in the membrane occurs, leading to vesicle clustering, with the appearance of elongated structures where both the lipid and the protein are present.

Structural and luminescence properties of Eu and Er implanted Bi2O3 nanowires for optoelectronic applications

Effective Er and Eu doping of α-Bi2O3 nanowires has been achieved by ion implantation. The nanostructures exhibit stable and efficient photoluminescence emission at room temperature after adequate annealing. X-ray photoelectron and X-ray absorption spectroscopy measurements reveal the incorporation of Er and Eu ions only in the desired trivalent charge state. The structural recovery of the implantation damage after thermal treatments was monitored by micro-Raman spectroscopy. Nanowires implanted with 300 keV ions and fluences in the range of 2 × 1015 to 8 × 1015 cm−2 show luminescence emission after annealing at 450 °C and 550 °C. Samples implanted with Eu ions show Eu3+ emission lines at 543 nm (5D1–7F1 transition), 587 nm (5D1–7F3 transition), 613 and 622 nm (5D0–7F2 transitions). Er-implanted nanowires show luminescence in the red range between 650 and 680 nm, corresponding to Er3+ 2F9/2–4I15/2 transitions. High angle annular dark field scanning transmission electron microscopy observations combined with energy dispersive X-ray microanalysis measurements reveal the formation of dopant-rich regions at higher fluences, leading to a reduced optical signal.