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.

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.

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.

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).

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.

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.

Superparamagnetic iron oxide nanoparticles (SPIONs) conjugated with lipase Candida antarctica A for biodiesel synthesis.

Biodiesel is an alternative biodegradable and non-toxic fuel, with a low emission profile and capable of reducing significantly the level of carcinogenic pollutants released into the atmosphere. A newly designed nano-biocatalyst prepared by conjugation of lipase A on superparamagnetic iron oxide nanoparticles (SPIONs) demonstrated high efficiency for production of biodiesel by the reaction of soybean oil with anhydrous methanol. The nanomaterial was characterized by FTIR, TGA and XRD, and its enzymatic activity compared with Lipozyme 435, a commercial gold standard from Novozyme™, which presented average enzymatic activity of 4559 ± 75 only twice as large as that of the SPION-CAL-A catalyst (2283 ± 249 PLU g-1), whereas Lipozyme TLIM showed a much lower activity of 588 ± 16 PLU g-1. These results were confirmed in the transesterification reaction for production of biodiesel where a yield of 11.4% was achieved with Lipozyme 435 and 4.6 ± 0.5% with the nano-biocatalyst. Such an improved performance associated with easy magnetic recovery and reuse make the material potentially interesting for production of biodiesel from used cooking oil, adding value to this abundant resource.

Decorated Superparamagnetic Iron Oxide Nanoparticles with Monoclonal Antibody and Diethylene-Triamine-Pentaacetic Acid Labeled with Thechnetium-99m and Galium-68 for Breast Cancer Imaging.

PURPOSE: In this study we developed and tested an iron oxide nanoparticle conjugated with DTPA and Trastuzumab, which can efficiently be radiolabeled with 99m-Tc and Ga-68, generating a nanoradiopharmaceutical agent to be used for SPECT and PET imaging. METHODS: The production of iron oxide nanoparticle conjugated with DTPA and Trastuzumab was made using phosphorylethanolamine (PEA) surface modification. Both radiolabeling process was made by the direct radiolabeling of the nanoparticles. The in vivo assay was done in female Balb/c nude mice xenografted with breast cancer. Also a planar imaging using the radiolabeled nanoparticle was performed. RESULTS: No thrombus and immune response leading to unwanted interaction and incorporation of nanoparticles by endothelium and organs, except filtration by the kidneys, was observed. In fact, more than 80% of 99mTc-DTPA-TZMB@Fe3O4 nanoparticles seems to be cleared by the renal pathway but the implanted tumor whose seems to increase the expression of HER2 receptors enhancing the uptake by all other organs. CONCLUSION: However, even in this unfavorable situation the tumor bioconcentrated much larger amounts of the nano-agent than normal tissues giving clear enough contrast for breast cancer imaging for diagnostics purpose by both SPECT and PET technique. Graphical Abstract ᅟ.

Ultrasmall cationic superparamagnetic iron oxide nanoparticles as nontoxic and efficient MRI contrast agent and magnetic-targeting tool.

Fully dispersible, cationic ultrasmall (7 nm diameter) superparamagnetic iron oxide nanoparticles, exhibiting high relaxivity (178 mM(-1)s(-1) in 0.47 T) and no acute or subchronic toxicity in Wistar rats, were studied and their suitability as contrast agents for magnetic resonance imaging and material for development of new diagnostic and treatment tools demonstrated. After intravenous injection (10 mg/kg body weight), they circulated throughout the vascular system causing no microhemorrhage or thrombus, neither inflammatory processes at the mesentery vascular bed and hepatic sinusoids (leukocyte rolling, adhesion, or migration as evaluated by intravital microscopy), but having been spontaneously concentrated in the liver, spleen, and kidneys, they caused strong negative contrast. The nanoparticles are cleared from kidneys and bladder in few days, whereas the complete elimination from liver and spleen occurred only after 4 weeks. Ex vivo studies demonstrated that cationic ultrasmall superparamagnetic iron oxide nanoparticles caused no effects on hepatic and renal enzymes dosage as well as on leukocyte count. In addition, they were readily concentrated in rat thigh by a magnet showing its potential as magnetically targeted carriers of therapeutic and diagnostic agents. Summarizing, cationic ultrasmall superparamagnetic iron oxide nanoparticles are nontoxic and efficient magnetic resonance imaging contrast agents useful as platform for the development of new materials for application in theranostics.

Titanium dioxide induced inflammation in the small intestine.

AIM: To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO2) and microparticles (MPTiO2) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO2 (100 mg/kg body weight) as NPTiO2 (66 nm), or MPTiO2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-ß (TGF-ß) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4+ cells (cells/mm²) in duodenum: NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum: NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum: NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-ß. The cytokine production was more pronounced in the ileum (mean ± SE): IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99 ± 019 (P < 0.05); IFNγ: NP 15.85 ± 9.99, MP 34.08 ± 11.44 vs 2.81 ± 0.69 (P < 0.05); and TGF-ß: NP 780.70 ± 318.50, MP 1409.00 ± 502.20 vs 205.50 ± 63.93 (P < 0.05). CONCLUSION: Our findings indicate that TiO2 particles induce a Th1-mediated inflammatory response in the small bowel in mice.