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An efficient drug delivery strategyis presented for novel anticanceramphiphilic ruthenium anionic complexes, based on the formation ofstable nanoparticles with the cationic lipid 1,2-dioleyl-3-trimethylammoniumpropanechloride (DOTAP). This strategy is aimed at ensuring high rutheniumcontent within the formulation, long half-life in physiological media,and enhanced cell uptake. An in-depth microstructural characterizationof the aggregates obtained mixing the ruthenium complex and the phospholipidcarrier at 50/50 molar ratio is realized by combining a variety oftechniques, including dynamic light scattering (DLS), small angleneutron scattering (SANS), neutron reflectivity (NR), electron paramagneticresonance (EPR), and zeta potential measurements. The in vitro bioactivityprofile of the Ru-loaded nanoparticles is investigated on human andnon-human cancer cell lines, showing IC50values in thelow μM range against MCF-7 and WiDr cells, that is, provingto be 10–20-fold more active than AziRu, a previously synthesizedNAMI-A analog, used for control. Fluorescence microscopy studies demonstratethat the amphiphilic Ru-complex/DOTAP formulations, added with rhodamine-B,are efficiently and rapidly incorporated in human MCF-7 breast adenocarcinomacells. The intracellular fate of the amphiphilic Ru-complexes wasinvestigated in the same in vitro model by means of an ad hoc designedfluorescently tagged analog, which exhibited a marked tendency toaccumulate within or in proximity of the nuclei. [ABSTRACT FROM AUTHOR]

Establishing structure–property relationshipsin the blackinsoluble eumelanins, the key determinants of human pigmentation andskin photoprotective system, is a considerable conceptual and experimentalchallenge in the current drive for elucidation of the biological rolesof these biopolymers and their application as advanced materials fororganoelectronics. Herein, we report a new breakthrough toward thisgoal by the first detailed investigation on the nanoscale level ofthe oxidative polymerization of 5,6-dihydroxyindole (DHI), a modelprocess of eumelanin synthesis. On the basis of a combined use ofspectrophotometry, dynamic light scattering (DLS), and small-angleneutron scattering (SANS) investigations, it was possible to unveilthe dynamics of the aggregation process before precipitation, thekey relationships with visible light absorption and the shape of fundamentalaggregates. The results indicated a polymerization mechanism of thetype: Polymern DHIx= Polymern,where DHIxindicates monomer, dimer, orlow oligomers (x≤ 5). During polymerization,visible absorption increases rapidly, reaching a plateau. Particlegrowth proceeds slowly, with formation of 2-D structures ∼55nm thick, until precipitation occurs, that is, when large aggregateswith a maximum hydrodynamic radius (Rh) of ∼1200 nm are formed. Notably, markedly smaller Rhvalues, up to ∼110 nm, were determinedin the presence of poly(vinyl alcohol) (PVA) that was shown to bean efficient aggregation-preventing agent for polymerizing DHI ensuringwater solubilization. Finally, it is shown that DHI monomer can beefficiently and partially irreversibly depleted from aqueous solutionsby the addition of eumelanin suspensions. This behavior is suggestedto reflect oxidant-independent competing pathways of polymer synthesisand buildup viamonomer conversion on the activeaggregate surface contributing to particle growth. Besides fillingcrucial gaps in DHI polymerization, these results support the attractivehypothesis that eumelanins may behave as a peculiar example of livingbiopolymers. The potential of PVA as a powerful tool for solutionchemistry-based investigations of eumelanin supramolecular organizationand for technological manipulation purposes is underscored. [ABSTRACT FROM AUTHOR]

Biocompatible poly( N-vinyl-2-pyrrolidone) (PVP) hydrogels have been produced by UV irradiation of aqueous polymer mixtures, using a high-pressure mercury lamp. The resulting materials have been characterized by a combination of experimental techniques, including rheology, small-angle neutron scattering (SANS), electron paramagnetic resonance (EPR), and pulsed gradient spin-echo nuclear magnetic resonance (PGSE-NMR), to put in evidence the relationship between the microstructural properties and the macrofunctional behavior of the gels. Viscoelastic measurements showed that UV photo-cross-linked PVP hydrogels present a strong gel mechanical behavior and viscoelastic moduli values similar to those of biological gels. The average distance between the cross-linking points of the polymer network was estimated from the hydrogels elastic modulus. However, SANS measurements showed that the network microstructure is highly inhomogeneous, presenting polymer-rich regions more densely cross-linked, surrounded by a water-rich environment. EPR and PGSE-NMR data further support the existence of these water-rich domains. Inclusion of a third component, such as glycerol, in the PVP aqueous mixture to be irradiated has been also investigated. A small amount of glycerol (<3% w/w) can be added keeping satisfactory properties of the hydrogel, while higher amounts significantly affect the cross-linking process.