Rational Understanding of Loading and Release of Doxorubicin by UV-Light- and pH-Responsive Poly(NIPAM-co-SPMA) Micelle-like Aggregates.

A deep understanding of the interactions between micelle-like aggregates and antineoplastic drugs is paramount to control their adequate delivery. Herein, Poly(NIPAM-co-SPMA) copolymer nanocarriers were synthesized according to our previous published methodology, and the loading and release of poorly and highly water-soluble doxorubicin forms (Dox and Dox-HCl, respectively) were evaluated upon UV light irradiation and pH-variation stimuli. Capillary electrophoresis (CE) coupled to a fluorescence detector (LIF) allowed us to specifically characterize these systems and deeply study the loading and release processes. For this purpose, varying concentrations of doxorubicin were tested, and the loading/release rates were indirectly quantified thanks to the "free" doxorubicin concentration in solution. This study highlighted that Dox loading (9.4 µg/mg) was more effective than Dox-HCl loading (5.5 µg/mg). In contrast, 68 and 74% of Dox-HCl were respectively released after 2 min upon pH variation (from 7.4 to 6.0) and combined UV + pH 6.0 stimuli, while only 27% of Dox was invariably released upon application of the same stimuli. These results are coherent with the characteristics of both DoxHCl and Dox: Electrostatic interactions between Dox-HCl and the micelle-membrane structure (NIPAM) seemed predominant, while hydrophobic interactions were expected between Dox and the SP moieties at the inner part of the micelle-like aggregate, leading to different behaviors in both loading and release of the two doxorubicin forms. For doxorubicin loading concentrations higher than 3 µM, the electrophoretic profiles presented an additional peak. Thanks to CE characterizations, this peak was attributed to the formation of a complex formed between the nonaggregated copolymer and the doxorubicin molecules. This report therefore undergoes deep characterization of the dynamic formation of different micelle/drug complexes involved in the global drug-delivery behavior and therefore contributes to the development of more effective stimuli-responsive nanocarriers.

Conducting Polymers in the Fields of Energy, Environmental Remediation, and Chemical-Chiral Sensors.

Conducting polymers (CPs), thanks to their unique properties, structures made on-demand, new composite mixtures, and possibility of deposit on a surface by chemical, physical, or electrochemical methodologies, have shown in the last years a renaissance and have been widely used in important fields of chemistry and materials science. Due to the extent of the literature on CPs, this review, after a concise introduction about the interrelationship between electrochemistry and conducting polymers, is focused exclusively on the following applications: energy (energy storage devices and solar cells), use in environmental remediation (anion and cation trapping, electrocatalytic reduction/oxidation of pollutants on CP based electrodes, and adsorption of pollutants) and finally electroanalysis as chemical sensors in solution, gas phase, and chiral molecules. This review is expected to be comprehensive, authoritative, and useful to the chemical community interested in CPs and their applications.

Simultaneous Electrochemical Speciation of Oxidized and Reduced Glutathione. Redox Profiling of Oxidative Stress in Biological Fluids with a Modified Carbon Electrode.

The simultaneous electrochemical quantification of oxidized (GSSG) and reduced glutathione (GSH), biomarkers of oxidative stress, is demonstrated in biological fluids. The detection was accomplished by the development of a modified carbon electrode and was applied to the analysis of biological fluids of model organisms under oxidative stress caused by lead intoxication. Nanocomposite molecular material based on cobalt phthalocyanine (CoPc) and multiwalled carbon nanotubes functionalized with carboxyl groups (MWCNTf) was developed to modify glassy carbon electrodes (GCE) for the detection of reduced and oxidized glutathione. The morphology of the nanocomposite film was characterized by scanning electron microscopy (SEM) and profilometry. The electrochemical behavior of the modified electrode was assessed by cyclic voltammetry (CV) to determine the surface coverage (Γ) by CoPc. The electrocatalytic behavior of the modified electrode toward reduced (GSH) and oxidized (GSSG) forms of glutathione was assessed by CV studies at physiological pH. The obtained results show that the combined use of CoPc and MWCNTf results in an electrocatalytic activity for GSH oxidation and GSSG reduction, enabling the simultaneous detection of both species. Differential pulse voltammetry reveals detection limits of 100 µM for GSH and 8.3 µM for GSSG, respectively. The potential interference from ascorbic acid, cysteine, glutamic acid, and glucose was also studied, and the obtained results show limited effects from these species. Finally, the hybrid electrode was used for the determination of GSH and GSSG in rat urine and plasma samples, intoxicated or not by lead. Both glutathione forms were detected in these complex biological matrixes without any pretreatment. Our results portray the role of GSH and GSSG as markers of oxidative stress in live organisms under lead intoxication.

Design, synthesis, and characterization of new cyclic d,l-α-alternate amino acid peptides by capillary electrophoresis coupled to electrospray ionization mass spectrometry.

The self-assembly of peptide nanotubes (PNTs) depends on the structure and chemistry of cyclic peptide (CP) monomers, having an impact on their properties, making the choice of their monomers and their characterization a great challenge. We synthesized for the first time a new set of eight original CP sequences of 8, 10, and 12 d,l-α-alternate amino acids with a controlled internal diameter from 7 to 13 Å. They present various properties (e.g., diameter, global surface charge, hydrophobicity) that can open the way to new applications. Their structure and purity were determined thanks to a capillary electrophoresis coupled to electrospray ionization mass spectrometry (CE-ESI-MS) methodology developed for the first time for this purpose. The CPs were successfully separated in a basic hydro-organic background electrolyte (BGE, pH 8.0, H2O/EtOH 50:50, v/v) and analyzed in MS positive mode. The effect of CP structure on electrophoretic mobility was studied, and the mass spectra were deeply analyzed. This methodology allowed verifying their purity and the absence of linear peptide precursors as well as their stability when stored over several months. Therefore, we have developed a new CE-ESI-MS methodology for the structure and purity control of interesting potential precursors for PNTs that could be employed as nanoplatforms in diagnostics or as pseudo sieving tools for separative purposes.

Critical Electrospinning Parameters for Synthesis Control of Stabilized Polyacrylonitrile Nanofibers.

Polyacrylonitrile (PAN) fibers are widely used as precursors in the manufacture of high-conducting and mechanically resistant carbon fibers. The modulation of such fibers is carried out through electrospinning. In this work, we show the production and control of the morphology of nanometric-range PAN fibers for their potential use as precursors for high-electrical-conductivity carbon fibers. PAN samples dissolved in dimethylformamide (DMF) were prepared at 6, 10, and 12% w/w, at 15 and 25 kV. The impact of the rotation of the collector drum at 100, 300, and 500 RPM was also studied. It was found that the percentage of PAN in the solution proportionally affects the diameter of the fibers and that the preparation potential affects the morphology. The rotation speed, when increased, decreases the diameter, and it has a negative impact on the morphology. Fibers prepared with 6% w/w at 15 kV and 500 RPM show 90 nm diameters, the smallest diameter of all the samples.

Electrochemical determination of Saccharomyces cerevisiae sp using glassy carbon electrodes modified with oxidized multi-walled carbon nanotubes dispersed in water -Nafion®.

The electrochemical behavior of Saccharomyces cerevisiae sp was studied using a glassy carbon electrode (GCE) modified with Nafion-dispersed oxidized multi-walled carbon nanotubes (OMWCNT). The morphology was studied using scanning electron microscopy (SEM), showing that the yeast sticks to the carbon nanotube surface instead of the glassy carbon surface. The redox couple Fe(CN)6 4-/Fe(CN)6 3- was used to determine the electroactive area and the heterogeneous transfer constant, which increased 80.5% and 108% respectively by the presence of nanotubes. The studies of the pH effect showed that the anodic potential decreases at alkaline pH and that the highest current intensity occurs at a pH value of 7.00. Studies of the scan rate effect have shown that yeast oxidation is an irreversible mixed control process in which two electrons participate. The relationship between yeast concentration and the anodic current density was studied using different electrochemical techniques obtaining the best analytical parameters through chronoamperometry. The linear range was between 3.36 and 6.52 g L-1, the limit of detection (LOD) and the limit of quantification (LOQ) were 0.98 g L-1 and 3.36 g L-1 respectively, and the sensibility obtained was 0.086 µA L g-1 mm-2. These results show that the multi-walled carbon nanotubes in water and Nafion® allow obtaining an anodic signal corresponding to the yeast, which facilitates its quantification through electrochemical methodologies, favoring the reduction of analysis times and costs compared with other techniques.

A novel coordination mode of κ1-N-Br-pyridylbenz-(imida, oxa or othia)-zole to Pt(ii): synthesis, characterization, electrochemical and structural analysis.

Herein, three novel Pt(ii) complexes with formula [trans-Pt(Br-PyBenz-X)(Cl)2(DMSO)] (1-3) having Br-pyridylbenz-(imida, oxa or othia)-zole (L1-3) derivatives as potential bidentate ligands, under an unusual κ1-N-coordination mode are reported. All compounds were obtained straightforwardly via reaction of corresponding LPB1-3 and [Pt(Cl)2(DMSO)2] (DMSO = dimethyl sulfoxide), at 100 °C in acetonitrile, respectively. 1-3 complexes were characterized by analytical and spectroscopic data: melting point, FT-IR, Raman, UV/Vis and NMR experiments. Cyclic voltammetry studies show an irreversible two-electron process at -0.50 and -0.51 V, which was ascribed to the Pt(ii)/Pt(iv) couple, for complexes 2 and 3. The crystal structure of complex 2 was elucidated by single-crystal X-ray diffraction, where the platinum atom exhibits a square plane geometry, where LPB2 adopts an unusual mono-coordinated mode via an N-κ1-benzoxazole ring. According to DFT calculations the first N-coordination exchanging one DMSO molecule is favourable, while the second N-coordination is highly impeded.

Efficient degradation of selected polluting dyes using the tetrahydroxoargentate ion, Ag(OH)4-, in alkaline media.

The use of soluble and highly oxidizing Ag(III) in the form of the tetrahydroxoargentate ion Ag(OH)4- is reported for the oxidation of surrogate organic recalcitrant dyes (i.e., rhodamine 6G (Rh6G) and fluorescein (Fl)). The possible use of Ag(OH)4- for the treatment of these and other refractory compounds is assessed. Such dyes were selected due to their common occurrence, stability, refractory nature, the relatively high toxicity of Rh6G, and their structural similarity to Fl. Several reaction intermediates/products were identified. The results showed that the highly oxidizing tetrahydroxoargentate anion was capable of degrading these recalcitrant dyes. Furthermore, the final degradation products do not represent a higher environmental risk than the original surrogates themselves. In addition, the partial mineralization of the dyes was proven.

Electrokinetic Hummel-Dreyer characterization of nanoparticle-plasma protein corona: The non-specific interactions between PEG-modified persistent luminescence nanoparticles and albumin.

Nanoparticles (NPs) play an increasingly important role in the development of new biosensors, contrast agents for biomedical imaging and targeted therapy vectors thanks to their unique properties as well as their good detection sensitivity. However, a current challenge in developing such NPs is to ensure their biocompatibility, biodistribution, bioreactivity and in vivo stability. In the biomedical field, the adsorption of plasmatic proteins on the surface of NPs impacts on their circulation time in blood, degradation, biodistribution, accessibility, the efficiency of possible targeting agents on their surface, and their cellular uptake. NP surface passivation is therefore a very crucial challenge in biomedicine. We developed herein for the first time an electrokinetic Hummel-Dreyer method to quantitatively characterize the formation of protein corona on the surface of NPs. This strategy was designed and optimized to evaluate the non specific binding of bovine serum albumin with the recently discovered PEG-functionalized ZnGa1.995Cr0.005O4 persistent luminescence NPs developed for in vivo biological imaging. The binding strength and the number of binding sites were determined at different ionic strengths. This methodology opens the way to an easy, low sample- and low time-consuming evaluation of the impact of NP surface modification on protein-corona formation and therefore on their potential for various bio-medical applications.

Photo-stimulation of persistent luminescence nanoparticles enhances cancer cells death.

Persistent luminescence nanoparticles made of ZnGa1.995Cr0.005O4 (ZGO-NPs) are innovative nanomaterials that emit photons during long periods of time after the end of the excitation, allowing their use as diagnosis probes for in vivo optical imaging. During the excitation process, a part of the energy is stored in traps to further emit photons over long time. However, we observed in this study that some of the energy reduces molecular oxygen to produce reactive oxygen species (ROS). Following this observation, theoxidative stress induction and cytotoxic effects of these NPs were investigated on human breast cancer cells. The results indicate that ROS production was stimulated by exposition of the hydroxylated ZGO-NPs to UV or visible light, and the oxidative stress induced in cells after internalization can be directly correlated to their dose-dependent inhibition of cell viability. On the contrary, PEGylated ZGONPs were not uptaken by cells and have no effect on the production of ROS. Thus, the cell viability was not altered by these nanoparticles. This study reveals the importance of considering light irradiation and surface coating of luminescent nanoparticles toxicity which open new perspectives for their use in photodynamic therapy.

Long-term toxicological effects of persistent luminescence nanoparticles after intravenous injection in mice.

The ZnGa1.995Cr0.005O4 persistent luminescence nanoparticles offer the promise of revolutionary tools for biological imaging with applications such as cell tracking or tumor detection. They can be re-excited through living tissues by visible photons, allowing observations without any time constraints and avoiding the undesirable auto-fluorescence signals observed when fluorescent probes are used. Despite all these advantages, their uses demand extensive toxicological evaluation and control. With this purpose, mice were injected with a single intravenous administration of hydroxylated or PEGylated persistent luminescence nanoparticles at different concentrations and then a set of standard tests were carried out 1day, 1 month and 6 months after the administration. High concentrations of hydroxylated nanoparticles generate structural alterations at histology level, endoplasmic reticulum damage and oxidative stress in liver, as well as rising in white blood cells counts. A mechanism involving the endoplasmic reticulum damage could be the responsible of the observed injuries in case of ZGO-OH. On the contrary, no toxicological effects related to PEGylated nanoprobes treatment were noted during our in vivo experiments, denoting the protective effect of PEG-functionalization and thereby, their potential as biocompatible in vivo diagnostic probes.

Functionalization and characterization of persistent luminescence nanoparticles by dynamic light scattering, laser Doppler and capillary electrophoresis.

Zinc gallate nanoparticles doped with chromium (III) (ZnGa1.995O4:Cr0.005) are innovative persistent luminescence materials with particular optical properties allowing their use for in vivo imaging. They can be excited in the tissue transparency window by visible photons and emit light for hours after the end of the excitation. This allows to observe the probe without any time constraints and without autofluorescence signals produced by biological tissues. Modification of the surface of these nanoparticles is essential to be colloidally stable not only for cell targeting applications but also for proper distribution in living organisms. The use of different methods for controlling and characterizing the functionalization process is imperative to better understand the subsequent interactions with biological elements. This work explores for the first time the characterization and optimization of a classic functionalization sequence, starting with hydroxyl groups (ZGO-OH) at the nanoparticle surface, followed by an aminosilane-functionalization intermediate stage (ZGO-NH2) before PEGylation (ZGO-PEG). Dynamic light scattering and laser doppler electrophoresis were used in combination with capillary electrophoresis to characterize the nanoparticle functionalization processes and control their colloidal and chemical stability. The hydrodynamic diameter, zeta potential, electrophoretic mobility, stability over time and aggregation state of persistent luminescence nanoparticles under physiological-based solution conditions have been studied for each functional state. Additionally, a new protocol to improve ZGO-NH2 stability based on a thermal treatment to complete covalent binding of (3-aminopropyl) triethoxysilane onto the particle surface has been optimized. This thorough control increases our knowledge on these nanoparticles for subsequent toxicological studies and ultimately medical application.

Melatonin attenuates the effects of sub-acute administration of lead on kidneys in rats without altering the lead-induced reduction in nitric oxide.

Exposure to lead induces oxidative stress and renal damage. Although most forms of oxidative stress are characterized by simultaneous elevation of nitrogen and oxidative species, lead-induced oxidative stress is unusual in that it is associated with a reduction in nitric oxide (NO) levels in the kidney. The role of NO in kidney injury is controversial; some studies suggest that it is associated with renal injury, whereas others show that it exerts protective effects. Concentration-dependent effects have also been proposed, linking low levels with vasodilatation and high levels with toxicity. The aim of this study was to evaluate the effects of melatonin co-exposure on the lead-induced reduction in renal NO levels. We found that sub-acute intraperitoneal administration of 10 mg/kg/day of lead for 15 days induced toxic levels of lead in the blood and caused renal toxicity (pathological and functional). Under our experimental conditions, lead induced an increase in lipid peroxidation and a decrease in NO. Melatonin co-treatment decreased lead-induced oxidative stress (peroxidation level) and toxic effects on kidneys without altering the lead-induced reduction in renal NO. These results suggest that, in our experimental model, the reduction in renal NO levels by lead exposure is not the only responsible factor for lead-induced kidney damage.

Electroreduction of Cr(VI) to Cr(III) on reticulated vitreous carbon electrodes in a parallel-plate reactor with recirculation.

The reduction of Cr(VI) to Cr(III) is achieved in a flow-by, parallel-plate reactor equipped with reticulated vitreous carbon (RVC) electrodes;this reduction can be accomplished by the application of relatively small potentials. Treatment of synthetic samples and field samples (from an electrodeposition plant) results in final Cr(VI) concentrations of 0.1 mg/L (i.e., the detection limit of the UV-vis characterization technique used here) in 25 and 43 min, respectively. Such concentrations comply with typical environmental legislation for wastewaters that regulate industrial effluents (at presenttime = 0.5 mg/L for discharges). The results show the influence of the applied potential, pH, electrode porosity, volumetric flow, and solution concentration on the Cr(VI) reduction percentage and on the required electrolysis time. Values for the mass transfer coefficient and current efficiencies are also obtained. Although current efficiencies are not high, the fast kinetics observed make this proposed treatment an appealing alternative. The lower current efficiency obtained in the case of a field sample is attributed to electrochemical activation of impurities. The required times for the reduction of Cr(VI) are significantly lower than those reported elsewhere.