Glassy carbon electrode modified with a film of tetraruthenated nickel(ii) porphyrin located in natural smectite clay's interlayer for the simultaneous sensing of dopamine, acetaminophen and tryptophan.

A supramolecular complex µ-meso-tetra(4-pyridyl) porphyrinate nickel(ii)tetrakis[bis(bipyridine)(chloro)ruthenium(ii)] ([NiTPyP{Ru(bipy)2Cl}4]4+) was intercalated into the interlayer space of natural smectite clay (shortened as Ba) collected in a Cameroonian deposit at Bagba hill. Physicochemical characterization of the resulting material using ultraviolet-visible spectroscopy (UV-vis), Fourier transform infrared (FTIR) spectroscopy, and X-ray diffraction (XRD) confirmed the intercalation of the porphyrin within the interlayer space of the clay. The intercalated clay was then used to form a stable thin film onto a glassy carbon electrode (GCE) by drop casting a suspension of the hybrid material. The GCE modified with the intercalated organoclay endowed the electrode with a larger electrochemically active surface area, good stability, high selectivity, and sensitivity toward dopamine (DA), acetaminophen (AC) and tryptophan (Trp). In addition, it was observed that the modified electrodes exhibited good and pH-dependent electrocatalytic properties toward these analytes. The simultaneous determination of DA, AC and Trp at [NiTPyP{Ru(bipy)2Cl}4]4+-Ba/GCE was thus possible without the interference of one analyte on the others, and the resulting calibration curve exhibits two segments for the three analytes. For DA, AC and Trp, the detection limits were found to be 0.8 µM, 0.3 µM and 0.3 µM, respectively. The [NiTPyP{Ru(bipy)2Cl}4]4+-Ba/GCE modified electrodes were successfully applied for the determination of AC in Paracetamol, a commercial product, and Trp in real pharmaceutical formulation samples.

Interactions Between Silver Nanoparticles and Culture Medium Biomolecules with Dose and Time Dependencies.

The interaction between silver nanoparticles (AgNPs) and molecules producing coronas plays a key role in cytotoxicity mechanisms. Once adsorbed coronas determine the destiny of nanomaterials in vivo, their effective deployment in the biomedical field requires a comprehensive understanding of the dynamic interactions of biomolecules with nanoparticles. In this work, we characterized 40 nm AgNPs in three different nutritional cell media at different molar concentrations and incubation times to study the binding mechanism of molecules on surface nanoparticles. In addition, their cytotoxic effects have been studied in three cell lineages used as tissue regeneration models: FN1, HUV-EC-C, RAW 264.7. According to the data, when biomolecules from DMEM medium were in contact with AgNPs, agglomeration and precipitation occurred. However, FBS medium proteins indicated the formation of coronas over the nanoparticles. Nonetheless, little adsorption of molecules around the nanoparticles was observed when compared to DMEM supplemented with 10% FBS. These findings indicate that when nanoparticles and bioproteins from supplemented media interact, inorganic salts from DMEM contribute to produce large bio-coronas, the size of which varies with the concentration and time. The static quenching mechanism was shown to be responsible for the fluorescence quenching of the bioprotein aggregates on the AgNPs surface. The calculated bioprotein-nanoparticle surface binding constants were on the order of 105 M-1 at 37 °C, with hydrophobic interactions driven by enthalpy and entropy playing a role, as confirmed by thermodynamic analysis. Cytotoxicity data showed a systematic degrowth in the viable cell population as the number of nanoparticles increased and the diameter of coronas decreased. Cytotoxic intervals associated with half decrease of cell population were established for AgNPs molar concentration of 75 µM for 24 h and 50 µM for 48 h. In summary, through the cytotoxicity mechanism of bio-coronas we are able to manipulate cells' expansion rates to promote specific processes, such inflammatory mechanisms, at different time instants.

Effect of nanocapsules containing docosahexaenoic acid in mice with chronic inflammation.

BACKGROUND: Omega 3 fatty acids, such as docosahexaenoic acid (DHA) have been widely consumed as supplements to control chronic inflammation. Nanocapsules containing DHA (MLNC-DHA-a1) were developed and showed excellent stability. Thus, our objective was to evaluate the effect of MLNC-DHA-a1 nanocapsules on biomarkers of chronic inflammation. METHODS: Cells viability was determined by flow cytometry. The uptake of MLNC-DHA-a1 nanocapsules by macrophages and their polarization were determined. In vivo, LDLr(-,-) mice were fed a Western diet to promote chronic inflammation and were treated with MLNC-DHA-a1 nanocapsules, intravenously injected via the caudal vein once a week for 8 weeks. RESULTS: MLNC-DHA-a1 nanocapsules decreased the concentration of TNFα (p = 0.02) in RAW 264.7 cells compared to the non-treated group (NT), with no changes in IL-10 (p = 0.29). The nanocapsules also exhibited an increase in the M2 (F4/80+ CD206) phenotype (p < 0.01) in BMDM cells. In vivo, no difference in body weight was observed among the groups, suggesting that the intervention was well tolerated. However, compared to the CONT group, MLNC-DHA-a1 nanocapsules led to an increase in IL-6 (90.45 ×13.31 pg/mL), IL-1ß (2.76 ×1.34 pg/mL) and IL-10 (149.88 ×2.51 pg/mL) levels in plasma. CONCLUSION: MLNC-DHA-a1 nanocapsules showed the potential to promote in vitro macrophage polarization and were well-tolerated in vivo. However, they also increased systemic pro-inflammatory cytokines. Therefore, considering that this immune response presents a limitation for clinical trials, further studies are needed to identify the specific compound in MLNC-DHA-a1 that triggered the immune response. Addressing this issue is essential, as MLNC-DHA-a1 tissue target nanocapsules could contribute to reducing chronic inflammation.

Theoretical investigation of solvent and oxidation/deprotonation effects on the electronic structure of a mononuclear Ru-aqua-polypyridine complex in aqueous solution.

Mononuclear polypyridine ruthenium (Ru) complexes can catalyze various reactions, including water splitting, and can also serve as photosensitizers in solar cells. Despite recent progress in their synthesis, accurately modeling their physicochemical properties, particularly in solution, remains challenging. Herein, we conduct a theoretical investigation of the structural and electronic properties of a mononuclear Ru-aqua polypyridine complex in aqueous solution, considering five of its possible oxidation/protonation states species: [RuII(H2O)(py)(bpy)2]2+, [RuII(OH)(py)(bpy)2]+, [RuIII(H2O)(py)(bpy)2]3+, [RuIII(OH)(py)(bpy)2]2+ and [RuIV(O)(py)(bpy)2]2+, where py = pyridine and bpy = 2,2'-bipyridine. At first, we investigate the impact of proton-coupled and non-coupled electron transfer reactions on the geometry and electronic structure of the complexes in vacuum and in solution, using an implicit solvent model. Then, using a sequential multiscale approach that combines quantum mechanics and molecular mechanics (S-QM/MM), we examine the explicit solvent effects on the electronic excitations of the complexes, and compare them with the experimental results. The complexes were synthesized, and their absorption spectra measured in aqueous solution. To accurately describe the QM interactions between the metal center and the aqueous ligand in the MM simulations, we developed new force field parameters for the Ru atom. We analyze the solvent structure around the complexes and account for its explicit influence on the polarization and electronic excitations of the complexes. Notably, accounting for the explicit solvent polarization effects of the first solvation shells is essential to correctly describe the energy of the electronic transitions, and the explicit treatment of the hydrogen bonds at the QM level in the excitation calculations improves the accuracy of the description of the metal-to-ligand charge-transfer bands. Transition density matrix analysis is used to characterize all electronic transitions in the visible and ultraviolet ranges according to their charge-transfer (CT) character. This study elucidates the electronic structure of those ruthenium polypyridyl complexes in aqueous solution and underscores the importance of precisely describing solvent effects, which can be achieved employing the S-QM/MM method.

Novel Gadolinium-Free Ultrasmall Nanostructured Positive Contrast for Magnetic Resonance Angiography and Imaging.

Nanostructured contrast agents are promising alternatives to Gd3+-based chelates in magnetic resonance (MR) imaging techniques. A novel ultrasmall paramagnetic nanoparticle (UPN) was strategically designed to maximize the number of exposed paramagnetic sites and r1 while minimizing r2, by decorating 3 nm titanium dioxide nanoparticles with suitable amounts of iron oxide. Its relaxometric parameters are comparable to those of gadoteric acid (GA) in agar phantoms, and the r2/r1 ratio of 1.38 at 3 T is close to the ideal unitary value. The strong and prolonged contrast enhancement of UPN before renal excretion was confirmed by T1-weighted MR images of Wistar rats after intravenous bolus injection. Those results associated with good biocompatibility indicate its high potential as an alternative blood-pool contrast agent to the GA gold standard for MR angiography, especially for patients with severe renal impairment.

Optical limiting in multilayer graphene films on a cobalt buffer-layer produced by the sputtering technique.

Multilayer graphene (MLG) thin films were produced by a sputtering technique on a cobalt buffer-layer prepared at 500°C and thermal annealed after the deposition. The transformation of amorphous carbon (C) to graphene occurs by diffusion of C atoms through the catalyst metal; then the C atoms dissolved in the metal are nucleated as graphene. The thicknesses of cobalt and MLG thin films were 55 and 54 nm, respectively, obtained by atomic force microscopy (AFM). Raman spectroscopy showed that the ratio between the Raman bands 2D and G (I 2D /I G ) was 0.4 for the graphene thin film that was annealed at 750°C for 25 min, indicating that the films obtained are MLG. The Raman results were corroborated by transmission electron microscopy analysis. AFM was used to determine the Co and C film thickness and roughness. Transmittance measurements at 980 nm as a function of input power from a continuous-wave diode laser showed that the obtained MLG films present large nonlinear absorption and can be used as optical limiters.

Antibacterial effect, cytotoxicity, and bond strength of a modified dental adhesive containing silver nanoparticles.

This study aimed to evaluate the antibacterial effect, cytotoxicity, and microtensile bond strength of an adhesive system containing silver nanoparticles (NAg). NAg was synthesized and incorporated (500 and 1000 ppm) into Scotchbond Multi-Purpose (SBMP) primer and bond. A microtensile bond test (µTBS) was performed after 24 h and 1 year. The adhesive interface was characterized using a confocal Raman microscope. The antibacterial activity was assessed using agar diffusion and biofilm inhibition assays (S. mutans). MTT assay was used to assess the cytotoxicity of NAg-conditioned culture media on human dental pulp stem cells (hDPSCs). The results were statistically analyzed using analysis of variance and Tukey's tests (α = .01). Incorporating 500 and 1000 ppm of NAg in the SBMP did not affect the µTBS after 24 h (p > 0.05). However, in the 1 year evaluation, 500 ppm presented the highest µTBS values (p < 0.05). The addition of NAg at 500 and 1000 ppm in the primer and bond led to larger inhibition halos and colony-forming units than the control (p < 0.05). For the unpolymerized and polymerized groups, the combination of primer and bond presented the highest cytotoxic effects on hDPSCs (p < 0.05). In conclusion, incorporating 500 or 1000 ppm of NAg into an etch-and-rinse adhesive system led to an antibacterial effect without altering the cytotoxicity. SBMP at 500 ppm presented a higher µTBS at 1 year.

Development of Annexin A1-surface-functionalized metal-complex multi-wall lipid core nanocapsules and effectiveness on experimental colitis.

Annexin A1 (AnxA1), a 37KDa protein, is secreted by inflammatory and epithelial cells and displays anti-inflammatory and wound healing activities in intestinal bowel diseases. Herein, we aimed to functionalize recombinant AnxA1 (AnxA1) on multi-wall lipid core nanocapsules (MLNC) and investigate its effectiveness on experimental colitis. MLNC were prepared by covering lipid core nanocapsules (LNC) with chitosan, which coordinates metals to specific protein chemisorption sites. Therefore, MLNC were linked to Zn2+ and AnxA1 was added to form MLNC-AnxA1. LNC, MLNC and MLNC-AnxA1 presented average size of 129, 152 and 163 nm, respectively, and similar polydispersity indexes (0.xx); incorporation of chitosan inverted the negative potential zeta; the coordination efficiency of AnxA1 was 92.22 %, and transmission electron microscope photomicrograph showed MLNC-AnxA1 had a spherical shape. The effectiveness of MLNC-AnxA1 was measured in Dextran Sulfate Sodium (DSS)-induced colitis in male C57BL/6 mice. DSS (2 % solution) was administered from days 1-6; saline, LNC, MLNC, MLNC-AnxA1 or AnxA1 were administered, once a day, by oral or intraperitoneal (i.p.) routes, from days 6-9. Clinical parameters of the disease were measured from day 0-10 and gut tissues were collected for histopathology, immunohistochemistry and flow cytometry analyses. Only i.p. treatment with MLNC-AnxA1 reduced weight loss, diarrhea and disease activity index, and prevented loss of colonic structure integrity; induced the switch of macrophages into M2 phenotype in the lamina propria; recovered the colonic histoarchitecture by decreasing dysplasia of crypts, inflammation and ulcerations; restored the expression of claudin-1 Zonna-occludens-1 tight junctions in the inflamed gut; and induced stem cell proliferation in intestinal crypts. Associated, data highlight the functionalization of MLNC with AnxA1 as a tool to improve the local actions of such protein in the inflamed gut by inducing resolution of inflammation and tissue repair.

A New Supramolecular Tetraruthenated Cobalt (II) Porphyrazine Displaying Outstanding Electrocatalytical Performance in Oxygen Evolution Reaction.

A new supramolecular electrocatalyst for Oxygen Evolution Reaction (OER) was synthesized from a central multibridging cobalt tetrapyridylporphyrazine (CoTPyPz) species by attaching four [Ru(bpy)2Cl]+ groups. Both CoTPyPz and the tetraruthenated cobalt porphyrazine species, TRuCoTPyPz, form very homogenous molecular films just by dropcasting their methanol solutions onto GCE electrodes. Such films exhibited low overpotentials for O2 evolution, e.g., 560 e 340 mV, respectively, displaying high stability, typically exceeding 15 h. The kinetic parameters obtained from the Tafel plots showed that the peripheral complexes are very important for the electrocatalytic activity. Hyperspectral Raman images taken along the electrochemical process demonstrated that the cobalt center is the primary active catalyst site, but its performance is enhanced by the ruthenium complexes, which act as electron-donating groups, in the supramolecular system.

Unraveling the acid-base characterization and solvent effects on the structural and electronic properties of a bis-bidentate bridging ligand.

Understanding the interactions and the solvent effects on the distribution of several species in equilibrium and how it can influence the 1H-NMR properties, spectroscopy (UV-vis absorption), and the acid-base equilibria can be especially challenging. This is the case of a bis-bidentate bridging ligand bis(2-pyridyl)-benzo-bis(imidazole), where the two pyridyl and four imidazolyl nitrogen atoms can be protonated in different ways, depending on the solvent, generating many isomeric/tautomeric species. Herein, we report a combined theoretical-experimental approach based on a sequential quantum mechanics/molecular mechanics procedure that was successfully applied to describe in detail the acid-base characterization and its effects on the electronic properties of such a molecule in solution. The calculated free-energies allowed the identification of the main species present in solution as a function of the solvent polarity, and its effects on the magnetic shielding of protons (1H-NMR chemical shifts), the UV-vis absorption spectra, and the acid-base equilibrium constants (pKas) in aqueous solution. Three acid-base equilibrium constants were experimentally/theoretically determined (pKa1 = 1.3/1.2, pKa2 = 2.1/2.2 and pKa5 = 10.1/11.3) involving mono-deprotonated and mono-protonated cis and trans species. Interestingly, other processes with pKa3 = 3.7 and pKa4 = 6.0 were also experimentally determined and assigned to the protonation and deprotonation of dimeric species. The dimerization of the most stable neutral species was investigated by Monte Carlo simulations and its electronic effects were considered for the elucidation of the UV-vis absorption bands, revealing transitions mainly with the charge-transfer characteristic and involving both the monomeric species and the dimeric species. The good matching of the theoretical and experimental results provides an atomistic insight into the solvent effects on the electronic properties of this bis-bidentate bridging ligand.

Wide visible-range activatable fluorescence ZnSe:Eu3+/Mn2+@ZnS quantum dots: local atomic structure order and application as a nanoprobe for bioimaging.

The development of QDs-based fluorescent bionanoprobe for cellular imaging fundamentally relies upon the precise knowledge of particle-cell interaction, optical properties of QDs inside and outside of the cell, movement of a particle in and out of the cell, and the fate of particle. We reported engineering and physicochemical characterization of water-dispersible Eu3+/Mn2+ co-doped ZnSe@ZnS core/shell QDs and studied their potential as a bionanoprobe for biomedical applications, evaluating their biocompatibility, fluorescence behaviour by CytoViva dual mode fluorescence imaging, time-dependent uptake, endocytosis and exocytosis in RAW 264.7 macrophages. The oxidation state and local atomic structure of the Eu dopant studied by X-ray absorption fine structure (XAFS) analysis manifested that the Eu3+ ions occupied sites in both ZnSe and ZnS lattices for the core/shell QDs. A novel approach was developed to relieve the excitation constraint of wide bandgap ZnSe by co-incorporation of Eu3+/Mn2+ codopants, enabling the QDs to be excited at a wide UV-visible range. The QDs displayed tunable emission colors by a gradual increase in Eu3+ concentration at a fixed amount of Mn2+, systematically enhancing the Mn2+ emission intensity via energy transfer from the Eu3+ to Mn2+ ion. The ZnSe:Eu3+/Mn2+@ZnS QDs presented high cell viability above 85% and induced no cell activation. The detailed analyses of QDs-treated cells by dual mode fluorescence CytoViva microscopy confirmed the systematic color-tunable fluorescence and its intensity enhances as a function of incubation time. The QDs were internalized by the cells predominantly via macropinocytosis and other lipid raft-mediated endocytic pathways, retaining an efficient amount for 24 h. The unique color tunability and consistent high intensity emission make these QDs useful for developing a multiplex fluorescent bionanoprobe, activatable in wide-visible region.

Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19: randomised trial.

The risk of contamination and dissemination by SARS-CoV-2 has a strong link with nasal, oral and pharyngeal cavities. Recently, our research group observed the promising performance of an anionic phthalocyanine derivative (APD) used in a mouthwash protocol without photoexcitation; this protocol improved the general clinical condition of patients infected with SARS-CoV-2. The present two-arm study evaluated in vitro the antiviral activity and cytotoxicity of APD. Additionally, a triple-blind randomized controlled trial was conducted with 41 hospitalized patients who tested positive for COVID-19. All the included patients received World Health Organization standard care hospital treatment (non-intensive care) plus active mouthwash (experimental group AM/n = 20) or nonactive mouthwash (control group NAM/n = 21). The adjunct mouthwash intervention protocol used in both groups consisted one-minute gargling/rinsing / 5 times/day until hospital discharge. Groups were compared considering age, number of comorbidities, duration of symptoms prior admission and length of hospital stay (LOS). The associations between group and sex, age range, presence of comorbidities, admission to Intensive care unit (ICU) and death were also evaluated. The in vitro evaluation demonstrated that APD compound was highly effective for reduction of SARS-CoV-2 viral load in the 1.0 mg/mL (99.96%) to 0.125 mg/mL (92.65%) range without causing cytotoxicity. Regarding the clinical trial, the median LOS of the AM group was significantly shortened (4 days) compared with that of the NAM group (7 days) (p = 0.0314). Additionally, gargling/rinsing with APD was very helpful in reducing the severity of symptoms (no ICU care was needed) compared to not gargling/rinsing with APD (28.6% of the patients in the NAM group needed ICU care, and 50% of this ICU subgroup passed way, p = 0.0207). This study indicated that the mechanical action of the protocol involving mouthwash containing a compound with antiviral effects against SARS-CoV-2 may reduce the symptoms of the patients and the spread of infection. The use of APD in a mouthwash as an adjuvant the hospital COVID-19 treatment presented no contraindication and reduced the hospital stay period.Trial registration: The clinical study was registered at REBEC-Brazilian Clinical Trial Register (RBR-58ftdj).

scFv-Anti-LDL(-)-Metal-Complex Multi-Wall Functionalized-Nanocapsules as a Promising Tool for the Prevention of Atherosclerosis Progression.

Atherosclerosis can be originated from the accumulation of modified cholesterol-rich lipoproteins in the arterial wall. The electronegative LDL, LDL(-), plays an important role in the pathogenesis of atherosclerosis once this cholesterol-rich lipoprotein can be internalized by macrophages, contributing to the formation of foam cells, and provoking an immune-inflammatory response. Herein, we engineered a nanoformulation containing highly pure surface-functionalized nanocapsules using a single-chain fragment variable (scFv) reactive to LDL(-) as a ligand and assessed whether it can affect the LDL(-) uptake by primary macrophages and the progression of atherosclerotic lesions in Ldlr -/- mice. The engineered and optimized scFv-anti-LDL(-)-MCMN-Zn nanoformulation is internalized by human and murine macrophages in vitro by different endocytosis mechanisms. Moreover, macrophages exhibited lower LDL(-) uptake and reduced mRNA and protein levels of IL1B and MCP1 induced by LDL(-) when treated with this new nanoformulation. In a mouse model of atherosclerosis employing Ldlr -/- mice, intravenous administration of scFv-anti-LDL(-)-MCMN-Zn nanoformulation inhibited atherosclerosis progression without affecting vascular permeability or inducing leukocytes-endothelium interactions. Together, these findings suggest that a scFv-anti-LDL(-)-MCMN-Zn nanoformulation holds promise to be used in future preventive and therapeutic strategies for atherosclerosis.

In vivo evaluation of toxicity and anti-inflammatory activity of iron oxide nanoparticles conjugated with ibuprofen.

Aim: The low solubility and consequent poor bioavailability of ibuprofen (IBU) is a major drawback that can be overcome by anchoring IBU on ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) as effective multifunctional carriers for drug delivery. Methods: USPIONs were conjugated with glycerol phosphate (USPION-GP) and also co-conjugated with IBU (USPION-GP/IBU), and their in vivo toxicity and anti-inflammatory effects investigated. Phosphate buffer saline (control), IBU, USPION-GP and USPION-GP/IBU were intravenously administered 15 min before lipopolysaccharide-induced peritonitis in male Balb/c mice. Results: 4 h later, USPION bioconjugates did not appear to have caused toxicity to blood leukocytes or caused alterations in the spleen, liver or kidneys. Also, they inhibited lipopolysaccharide-induced neutrophil mobilization into the peritoneum. Conclusion: The absence of systemic toxicity and the unexpected anti-inflammatory action of USPION bioconjugates indicates that they could be a novel and effective approach to administer IBU and warrant further investigation.

A Phthalocyanine Derivate Mouthwash to Gargling/Rinsing as an Option to Reduce Clinical Symptoms of COVID-19: Case Series.

AIM: This case series demonstrated that phthalocyanine derivate mouthwash is a promising alternative for reducing the viral load of SARS-CoV-2 and for clinical improvement of infected patients who presented mild and moderate symptoms. PURPOSE: The aim of this study was to report a case series of patients diagnosed with COVID-19 that used the phthalocyanine derivate mouthwash to reduce clinical symptoms. PATIENTS AND METHODS: Eight patients used 5mL of phthalocyanine derivate mouthwash gargling/rinsing for one minute, five times daily, over a fourteen day period. Two measurement scales were applied for each patient in different periods to verify sore throat - VAS - Visual Analogue Scale for Pain and the clinical conditions - PS - Performance Status. RESULTS: All patients presented a significant reduction in clinical symptoms with the use of the mouthwash for gargling/rinsing after few days of use, without hospitalization. CONCLUSION: The phthalocyanine derivate mouthwash protocol appears as a potential alternative for clinical improvement of COVID-19 infected patients. Daily use of this mouthwash rapidly reduced clinical symptoms such as sore throats, cough and mouth ulcers. Large, high-quality randomized controlled trials with larger sample size are necessary to confirm the effectiveness of this mouthwash protocol against COVID-19.

Cytotoxicity of Methotrexate Conjugated to Glycerol Phosphate Modified Superparamagnetic Iron Oxide Nanoparticles.

A systematic study was carried out to evaluate the uptake and cytotoxicity of methotrexate (MTX) conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) modified with glycerol phosphate (Glyc) and phosphorylethanolamine (PEA), using MCF-7 cancer cell line as model. The ligand shell composition was controlled in such a way to get SPIONs with nine different surface functionalization and up to three co-conjugated ligands but the very iron oxide core, in order to test and compare uptake and cytotoxicity, and verify possible additive effects. Folic acid (FA), the non-toxic analogue of MTX, was also explored as ligand for SPIONs. Glyc was shown to enhance dramatically the cellular uptake despite the high negative zeta potentials, whereas PEA, FA and MTX was found to have a much lower effect on the cellular uptake. Also, a significant ten times lowering of IC50 was observed for the co-conjugated MTX in the SPION-Glyc/PEA/MTX as compared to the free drug, whereas the analogue SPION-Glyc/PEA/FA nanoparticles exhibited no significant cytotoxicity. In short, the conjugation of MTX to SPIONs enhanced dramatically its cytotoxicity and decreased the IC50 value against MCF-7 tumor cells as compared to the free drug, probably due to the enhanced uptake of SPIONs as a result of their surface modification with Glyc/PEA, demonstrating that SPION-Glyc/PEA is a good nanocarrier for co-conjugated methotrexate.

Combined Colorimetric and Electrochemical Measurement Paper-Based Device for Chemometric Proof-of-Concept Analysis of Cocaine Samples.

Cocaine (COC) is one of the most widely consumed illegal drugs around the world. Street COC is commonly adulterated with pharmaceutical compounds that mimic or intensify the COC's sensory effect. Adulteration is performed to increase the profit of criminal organizations and each one has their own way of doing it. Therefore, determining the composition of seized COC samples (chemical profile) provides evidence for the police to track criminal organization networks and their activity patterns. Using filter paper as a substrate, we developed a multiple detection paper-based analytical device (PAD) that combines colorimetric and electrochemical measurements to discriminate COC samples according to adulterant's content. A regular graphite lead modified with a gold film made from Au leaf (graphite/Au) to improve electron transfer was used as a working electrode. Silver and Ag/AgCl were used as auxiliary and reference electrodes, respectively. The colorimetric device was patterned using a laser cutter and coupled to the electrochemical device using a double-sided tape, allowing simultaneous analysis to gather more analytical information about COC samples. Graphite/Au was characterized by scanning and transmission electron microscopies and electrochemical assays. The simultaneous colorimetric and electrochemical analyses combined to principal component analysis improved the analytical characterization of COC trial samples and provided a fast discrimination based on the assembled database.

Silver Enhances Hematite Nanoparticles Based Ethanol Sensor Response and Selectivity at Room Temperature.

Gas sensors are fundamental for continuous online monitoring of volatile organic compounds. Gas sensors based on semiconductor materials have demonstrated to be highly competitive, but are generally made of expensive materials and operate at high temperatures, which are drawbacks of these technologies. Herein is described a novel ethanol sensor for room temperature (25 °C) measurements based on hematite (α­Fe2O3)/silver nanoparticles. The AgNPs were shown to increase the oxide semiconductor charge carrier density, but especially to enhance the ethanol adsorption rate boosting the selectivity and sensitivity, thus allowing quantification of ethanol vapor in 2-35 mg L-1 range with an excellent linear relationship. In addition, the α-Fe2O3/Ag 3.0 wt% nanocomposite is cheap, and easy to make and process, imparting high perspectives for real applications in breath analyzers and/or sensors in food and beverage industries. This work contributes to the advance of gas sensing at ambient temperature as a competitive alternative for quantification of conventional volatile organic compounds.

Phosphotungstic acid impregnated niobium coated superparamagnetic iron oxide nanoparticles as recyclable catalyst for selective isomerization of terpenes.

Conversion efficiency as high as 80-100% and 50% selectivity for camphene and limonene was achieved with low production of polymeric byproducts (18-28%), easy recovery with a magnet and reuse for up to five cycles maintaining similar activity and distribution of products, using a new magnetically recyclable catalyst based on niobium oxide coated on superparamagnetic iron oxide nanoparticles (SPION) impregnated with phosphotungstic acid (HPW). The catalyst was demonstrated to be effective in the selective conversion of alpha and beta-pinenes into valuable terpenes, under ultrasonic probe activation and with toluene as solvent. A unique synergic effect between the components generating more active and selective catalytic sites was demonstrated, indicating that the SPION covered with 30 wt% of Nb2O5 gives the best performance when impregnated with HPW as co-catalyst. The materials were fully characterized by XRD, EDX, XPS, TEM, BET, VSM and FTIR.

Multivariate probing of antitumor metal-based complexes damage on living cells through Raman imaging.

Intracellular modifications caused by two metal-based antitumor compounds were assessed by confocal Raman imaging assisted by multivariate curve resolution method, a very powerful deconvolution tool that can be used to extract the characteristic spectral profile of the individual or "purest" components from an image dataset. The use of this Raman methodology has the advantage of being non-invasive and totally label-free. Four main different intracellular processes were observed under the Raman imaging and multivariate approach combination, and even, significant differences could be identified between the treatments with both metallodrugs. Leakage of the nucleus and nucleolus content into the cytoplasm, along with releasing of cytochrome c were observed for the treatment with the Cu-based complex. At the same time, changes of hydrogen-bonding network were also evidenced, indicating an apoptotic cellular death process, consistent with complementary Total Reflection X-Ray fluorescence (TXRF) and fluorescence experiments attesting mitochondria and DNA as main targets after uptake of the complex by cells. For treatment with the Zn-based complex, changes associated with cytochrome c were not detected, neither a rapid leakage of nucleus content upon 24 h treatment. The hydrogen-bonding network also followed a quite different pattern, suggesting that with this metallodrug, the cellular death follows a different mechanism.