A novel and economical approach for the synthesis of short rod-shaped mesoporous silica nanoparticles from coal fly ash waste by Bacillus circulans MTCC 6811.

Coal fly ash (CFA) is an industrial byproduct produced during the production of electricity in thermal power plants from the burning of pulverized coal. It is considered hazardous due to the presence of toxic heavy metals while it is also considered valuable due to the presence of value-added minerals like silicates, alumina, and iron oxides. Silica nanoparticles' demands and application have increased drastically in the last decade due to their mesoporous nature, high surface area to volume ratio, etc. Here in the present research work, short rod-shaped, mesoporous silica nanoparticles (MSN) have been synthesized from coal fly ash by using Bacillus circulans MTCC 6811 in two steps. Firstly, CFA was kept with the bacterial culture for bioleaching for 25 days in an incubator shaker at 120 rpm. Secondly, the dissolved silica in the medium was precipitated with the 4 M sodium hydroxide to obtain a short rod-shaped MSN. The purification of the synthesized silica particle was done by treating them with 1 M HCl at 120 °C, for 90 min. The synthesized short rod-shaped MSN were characterized by UV-vis spectroscopy (UV-Vis), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Particle size analyzer (PSA), Field emission scanning electron microscopy (FESEM), and transmission electron microscope. The microscopic techniques revealed the short rod-shaped mesoporous silica nanoparticles (MSN) for the final nano-silica, whose size varies from 40 to 80 nm, with an average size of 36 ± 5 nm. The XRD shows the crystalline nature of the synthesized MSN having a crystallite size of 36 nm. The FTIR showed the three characteristic bands in the range of 400-1100 cm-1, indicating the purity of the sample. The energy dispersive X-ray (EDX) showed 53.04 wt% oxygen and 43.42% Si along with 3.54% carbon in the final MSN. The particle size analyzer revealed that the average particle size is 368.7 nm in radius and the polydispersity index (PDI) is 0.667. Such a novel and economical approach could be helpful in the synthesis of silica in high yield with high purity from coal fly ash and other similar waste.

Assessment of Occupational Exposure to Indium Dust for Indium-Tin-Oxide Manufacturing Workers.

According to recent research, indium nanoparticles (NPs) are more toxic than micro-sized particles. While cases of indium lung disease have been reported worldwide, very little research has been conducted on the occupational exposure to indium NPs. Recently, an indium-related lung disease was reported in Korea, a global powerhouse for display manufacturing. In this study, we conducted an assessment ofoccupational exposure at an indium tin oxide (ITO) powder manufacturing plant, where the first case of indium lung disease in Korea occurred. Airborne dustwas obtained from a worker's breathing zone, and area sampling in the workplace environment was conducted using real-time monitoring devices. Personal samples were analyzed for the indium concentrations in total dust, respirable dust fraction, and NPs using personal NPs respiratory deposition samplers. The total indium concentration of the personal samples was lower than the threshold limit value recommended by the American Conference of Governmental Industrial Hygienists (ACGIH TLV), which was set as occupational exposure limit (OEL). However, the respirable indium concentration exceeded the recently set ACGIH TLV for the respirable fraction of indium dust. The concentration of indium NPs ranged between 0.003 and 0.010 × 10-2 mg/m3, accounting for only 0.4% of the total and 2.7% of the respirable indium particles. This was attributed to the aggregating of NPs at the µm sub-level. Given the extremely low fraction of indium NPs in the total and respirable dust, the current OEL values, set as the total and respirable indium concentrations, do not holistically represent the occupational exposure to indium NPs or prevent health hazards. Therefore, it is necessary to set separate OEL values for indium NPs. This study covers only the process of handling ITO powder. Therefore, follow-up studies need to be conducted on other ITO sputtering target polishing and milling processes, which typically generate more airborne NPs, to further investigate the effects of indium on workers and facilitate the necessary implementation of indium-reducing technologies.

Entrapment of nano-ZnO into alginate/polyvinyl alcohol beads with different crosslinking ions for fertilizer applications.

Zinc oxide nanoparticles (nano-ZnO) are attractive as fertilizer materials but high concentrations may negatively affect the environment. To reduce their dispersion in the environment we entrapped nano-ZnO in biodegradable polymer beads consisting of alginate and polyvinyl alcohol (PVA). The alginate/PVA/ZnO beads were prepared via ionotropic gelation using two different crosslinking ions (Ca2+ and Zn2+), and the effect of alginate crosslinking ion and PVA content on bead structure, water absorption, water retention and zinc release was investigated. The pure CaAlg and ZnAlg beads demonstrated a poor water absorption and retention, which were strongly enhanced by the incorporation of PVA into the beads. The continuous Zn release was measured in a sand column, and it was found that the Zn-crosslinked beads rapidly released high concentrations of Zn followed by a more gradual Zn release, whereas Ca alginates showed only a gradual Zn release. The Zn dissolution kinetics could be tuned by the crosslinking ion composition. The prepared nano-ZnO-containing alginate/PVA beads may be attractive for Zn fertilizer applications under water-limited conditions.

Automation and low-cost proteomics for characterization of the protein corona: experimental methods for big data.

Nanoparticles used in biological settings are exposed to proteins that adsorb on the surface forming a protein corona. These adsorbed proteins dictate the subsequent cellular response. A major challenge has been predicting what proteins will adsorb on a given nanoparticle surface. Instead, each new nanoparticle and nanoparticle modification must be tested experimentally to determine what proteins adsorb on the surface. We propose that any future predictive ability will depend on large datasets of protein-nanoparticle interactions. As a first step towards this goal, we have developed an automated workflow using a liquid handling robot to form and isolate protein coronas. As this workflow depends on magnetic separation steps, we test the ability to embed magnetic nanoparticles within a protein nanoparticle. These experiments demonstrate that magnetic separation could be used for any type of nanoparticle in which a magnetic core can be embedded. Higher-throughput corona characterization will also require lower-cost approaches to proteomics. We report a comparison of fast, low-cost, and standard, slower, higher-cost liquid chromatography coupled with mass spectrometry to identify the protein corona. These methods will provide a step forward in the acquisition of the large datasets necessary to predict nanoparticle-protein interactions.

An open source and reduce expenditure ROS generation strategy for chemodynamic/photodynamic synergistic therapy.

The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H2O2) in chemodynamic therapy (CDT). Here, we report a H2O2/O2 self-supplying nanoagent, (MSNs@CaO2-ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO2) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO2 reacts with water to produce O2 and H2O2 for hypoxia-relieved ICG-mediated PDT and H2O2-supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies.

Mitigation of Rheumatic Arthritis in a Rat Model via Transdermal Delivery of Dapoxetine HCl Amalgamated as a Nanoplatform: In vitro and in vivo Assessment.

PURPOSE: Dapoxetine HCl (DH), a selective serotonin reuptake inhibitor, may be useful for the treatment of rheumatic arthritis (RA). The purpose of this study was to investigate the therapeutic efficacy of transdermal delivery of DH in transethosome nanovesicles (TENVs). This novel delivery of DH may overcome the drawbacks associated with orally administered DH and improve patient compliance. METHODS: DH-TENV formulations were prepared using an injection- sonication method and optimized using a 33 Box-Behnken-design with Design Expert® software. The TENV formulations were assessed for entrapment efficiency (EE-%), vesicle size, zeta potential, in vitro DH release, and skin permeation. The tolerability of the optimized DH-TENV gel was investigated using a rat skin irritation test. A pharmacokinetic analysis of the optimized DH-TENV gel was also conducted in rats. Moreover, the anti-RA activity of the optimized DH-TENV gel was assessed based on the RA-specific marker anti-cyclic cirtullinated peptide antibody (anti-CCP), the cartilage destruction marker cartilage oligomeric matrix protein (COMP) and the inflammatory marker interleukin-6 (IL-6). Level of tissue receptor activator of nuclear factor kappa-Β ligand (RANKL) were also assessed. RESULTS: The optimized DH-TENV formulation involved spherical nanovesicles that had an appropriate EE- % and skin permeation characteristic. The DH-TENV gel was well tolerated by rats. The pharmacokinetics analysis showed that the optimized DH-TENV gel boosted the bioavailability of the DH by 2.42- and 4.16-fold compared to the oral DH solution and the control DH gel, respectively. Moreover, it significantly reduced the serum anti-CCP, COMP and IL-6 levels and decreased the RANKL levels. Furthermore, the DH-TENV gel attenuated histopathological changes by almost normalizing the articular surface and synovial fluid. CONCLUSION: The results indicate that DH-TENVs can improve transdermal delivery of DH and thereby alleviate RA.

A novel bioactive nanoparticle synthesized by conjugation of 3-chloropropyl trimethoxy silane functionalized Fe3O4 and 1-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)-2-(4-phenylthiazol-2-yl) hydrazine: assessment on anti-cancer against gastric AGS cancer cells.

Gastric cancer is one of the common types of cancer around the world which has few therapeutic options. Nitrogen heterocyclic derivatives such as thiazoles are used as the basis for the progression of the drugs. The objective of this study was to synthesize the 1-((3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl) methylene)-2-(4-phenylthiazol-2-yl) hydrazine (TP) conjugating with (3-Chloropropyl) trimethoxysilane (CPTMOS)-coated Fe3O4 nanoparticles (NPs) for anti-cancer activities against gastric AGS cancer cell line. The synthesized Fe3O4@CPTMOS/TP NPs were characterized by FT-IR, XRD, EDX, SEM, TEM and Zeta potential analyses. To evaluate the toxicity of the above compound after AGS cell culture in RPMI1640 medium, the cells were treated at different concentrations for 24 h. The viability of the cells was investigated by MTT assay. Moreover, apoptosis induced by Fe3O4@CPTMOS/TP NPs was assessed by Hoechst 33432 staining, oxygen activity specification evaluation, caspase-3 activity assay, cell cycle analysis and annexin V/PI staining followed by flow cytometry analysis. The IC50 value in AGS cells was estimated to be 95.65 µg/ml. The flow cytometry results of Fe3O4@CPTMOS/TP NPs revealed a large number of cells in the apoptotic regions compared to the control cells and the cells treated with TP. In addition, the amount of ROS production and caspase-3 activity increased in the treated cells with Fe3O4@CPTMOS/TP NPs. The percentage of inhibited cancer cells in the G0/G1 phase increased under the treatment in the binding state to the nonionic iron oxide nanoparticles. Overall, this study showed that Fe3O4@CPTMOS/TP NP had effect on induction of apoptosis and inhibiting the growth of AGS cancer cells. Thus, Fe3O4@CPTMOS/TP NP can be considered as a new anti-cancer candid for next phase of studies on mouse models.

Nano-Fe3C@PGC as a novel low-cost anode electrocatalyst for superior performance microbial fuel cells.

We report a novel anode electrocatalyst, iron carbide nanoparticles dispersed in porous graphitized carbon (Nano-Fe3C@PGC), which is synthesized by facile approach involving a direct pyrolysis of ferrous gluconate and a following removal of free iron, but provides microbial fuel cells with superior performances. The physical characterizations confirm the unique configuration of iron carbide nanoparticles with porous graphitized carbon. Electrochemical measurements demonstrate that the as-synthesized Nano-Fe3C@PGC exhibits an outstanding electrocatalytic activity toward the charge transfer between bacteria and anode. Equipped with Nano-Fe3C@PGC, the microbial fuel cells based on a mixed bacterium culture yields a power density of 1856 mW m-2. The resulting excellent performance is attributed to the large electrochemical active area and the high electronic conductivity that porous graphitized carbon provides and the enriched electrochemically active microorganisms and enhanced activity towards the redox reactions in microorganisms by Fe3C nanoparticles.

Selenium nanoparticles as anti-infective implant coatings for trauma orthopedics against methicillin-resistant Staphylococcus aureus and epidermidis: in vitro and in vivo assessment.

Background: Bacterial infection is a common and serious complication in orthopedic implants following traumatic injury, which is often associated with extensive soft tissue damage and contaminated wounds. Multidrug-resistant bacteria have been found in these infected wounds, especially in patients who have multi trauma and prolonged stay in intensive care units.Purpose: The objective of this study was to develop a coating on orthopedic implants that is effective against drug-resistant bacteria. Methods and results: We applied nanoparticles (30-70nm) of the trace element selenium (Se) as a coating through surface-induced nucleation-deposition on titanium implants and investigated the antimicrobial activity against drug resistant bacteria including Methicillin-resistant Staphylococcus aureus (MRSA) and Methicillin-resistant Staphylococcus epidermidis (MRSE) in vitro and in an infected femur model in rats.The nanoparticles were shown in vitro to have antimicrobial activity at concentrations as low as 0.5ppm. The nanoparticle coatings strongly inhibited biofilm formation on the implants and reduced the number of viable bacteria in the surrounding tissue following inoculation of implants with biofilm forming doses of bacteria. Conclusion: This study shows a proof of concept for a selenium nanoparticle coatings as a potential anti-infective barrier for orthopedic medical devices in the setting of contamination with multi-resistant bacteria. It also represents one of the few (if only) in vivo assessment of selenium nanoparticle coatings on reducing antibiotic-resistant orthopedic implant infections.

Magnesium-zinc scaffold loaded with tetracycline for tissue engineering application: In vitro cell biology and antibacterial activity assessment.

Recently, porous magnesium and its alloys are receiving great consideration as biocompatible and biodegradable scaffolds for bone tissue engineering application. However, they presented poor antibacterial performance and corrosion resistance which limited their clinical applications. In this study, Mg-Zn (MZ) scaffold containing different concentrations of tetracycline (MZ-xTC, x = 1, 5 and 10%) were fabricated by space holder technique to meet the desirable antibacterial activity and corrosion resistance properties. The MZ-TC contains total porosity of 63-65% with pore sizes in the range of 600-800 µm in order to accommodate bone cells. The MZ scaffold presented higher compressive strength and corrosion resistance compared to pure Mg scaffold. However, tetracycline incorporation has less significant effect on the mechanical and corrosion properties of the scaffolds. Moreover, MZ-xTC scaffolds drug release profiles show an initial immediate release which is followed by more stable release patterns. The bioactivity test reveals that the MZ-xTC scaffolds are capable of developing the formation of HA layers in simulated body fluid (SBF). Next, Staphylococcus aureus and Escherichia coli bacteria were utilized to assess the antimicrobial activity of the MZ-xTC scaffolds. The findings indicate that those scaffolds that incorporate a high level concentration of tetracycline are tougher against bacterial organization than MZ scaffolds. However, the MTT assay demonstrates that the MZ scaffolds containing 1 to 5% tetracycline are more effective to sustain cell viability, whereas MZ-10TC shows some toxicity. The alkaline phosphatase (ALP) activity of the MZ-(1-5)TC was considerably higher than that of MZ-10TC on the 3 and 7 days, implying higher osteoblastic differentiation. All the findings suggest that the MZ-xTC scaffolds containing 1 to 5% tetracycline is a promising candidate for bone tissue healing due to excellent antibacterial activity and biocompatibility.

In Vitro Assessment of Fluorine Nanoemulsion-Labeled Hyaluronan-Based Hydrogels for Precise Intrathecal Transplantation of Glial-Restricted Precursors.

PURPOSE: We studied the feasibility of labeling hydrogel scaffolds with a fluorine nanoemulsion for 19F- magnetic resonance imaging (MRI) to enable non-invasive visualization of their precise placement and potential degradation. PROCEDURE: Hyaluronan-based hydrogels (activated hyaluronan, HA) with increasing concentrations of fluorine nanoemulsion (V-sense) were prepared to measure the gelation time and oscillatory stress at 1 h and 7 days after the beginning of gelation. All biomechanical measurements were conducted with an ARES 2 rheometer. Diffusion of fluorine from the hydrogel: Three hydrogels in various Vs to HA volumetric ratios (1:50, 1:10, and 1:5) were prepared in duplicate. Hydrogels were incubated at 37 °C. To induce diffusion, three hydrogels were agitated at 1000 rpm. 1H and 19F MRI scans were acquired at 1, 3, 7 days and 2 months after gel preparation on a Bruker Ascend 750 scanner. To quantify fluorine content, scans were analyzed using Voxel Tracker 2.0. Assessment of cell viability in vitro and in vivo: Luciferase-positive mouse glial-restricted progenitors (GRPs) were embedded in 0:1, 1:50, 1:10, and 1:5 Vs:HA mixtures (final cell concentration  =1 × 107/ml). For the in vitro assay, mixtures were placed in 96-wells plate in triplicate and bioluminescence was measured after 1, 3, 7, 14, 21, and 28 days. For in vivo experiments, Vs/HA mixtures containing GRPs were injected subcutaneously in SCID mice and BLI was acquired at 1, 3, 7, and 14 days post-injection. RESULTS: Mixing of V-sense at increasing ratios of 1:50, 1:10, and 1:5 v/v of fluorine/activated hyaluronan (HA) hydrogel gradually elongated the gelation time from 194 s for non-fluorinated controls to 304 s for 1:5 V-sense:HA hydrogels, while their elastic properties slightly decreased. There was no release of V-sense from hydrogels maintained in stationary conditions over 2 months. The addition of V-sense positively affected in vitro survival of scaffolded GRPs in a dose-dependent manner. CONCLUSIONS: These results show that hydrogel fluorination does not impair its beneficial properties for scaffolded cells, which may be used to visualize scaffolded GRP transplants with 19F MRI.

An assessment of the cytotoxic effects of graphene nanoparticles on the epithelial cells of the human lung.

Nanomaterials are widely used nowadays in a range of technological and biomedical fields. Graphene as a nanomaterial used in the health-care sector and in workplaces has raised some concerns about its toxicity. This study aimed to evaluate the cytotoxicity of graphene nanoparticles (GNPs) on the A549 epithelial cells of the human lung. The GNPs were synthesized from graphite by the modified Hummer method. The physicochemical characteristics of GNPs were identified by the transmission electron microscope, the scanning electron microscope, and the Brunauer-Emmett-Teller method. The hydrodynamic size of GNPs in the dispersion media was examined using the dynamic light scattering technique. The GNPs were dispersed, after which the A549 cells were cultured. Finally, the cell viability was assayed by the MTT assay. The statistical analysis of variance was used to describe the relationship between the concentration/time variables and the GNP-induced cell deaths. The probit regression model was also used to achieve toxicological indicators. The results showed that the toxicological effects of GNPs on the A549 epithelial cells of the human lung are dose- and time-dependent. The GNPs were more cytotoxic after a 72-h exposure period compared to a 24-h and 48-h exposure period. The inhibitory concentration of 50% and "no observed adverse effect concentration" were estimated to be 40,653.1 and 0.059 µg/mL, respectively. The results of this study can be helpful in developing the occupational exposure limit for GNPs and in improving occupational health programs in workplaces. However, more investigation is needed to specify the toxicological mechanisms of GNPs.

Assessment of in vitro particle dosimetry models at the single cell and particle level by scanning electron microscopy.

BACKGROUND: Particokinetic models are important to predict the effective cellular dose, which is key to understanding the interactions of particles with biological systems. For the reliable establishment of dose-response curves in, e.g., the field of pharmacology and toxicology, mostly the In vitro Sedimentation, Diffusion and Dosimetry (ISDD) and Distorted Grid (DG) models have been employed. Here, we used high resolution scanning electron microscopy to quantify deposited numbers of particles on cellular and intercellular surfaces and compare experimental findings with results predicted by the ISDD and DG models. RESULTS: Exposure of human lung epithelial A549 cells to various concentrations of differently sized silica particles (100, 200 and 500 nm) revealed a remarkably higher dose deposited on intercellular regions compared to cellular surfaces. The ISDD and DG models correctly predicted the areal densities of particles in the intercellular space when a high adsorption ("stickiness") to the surface was emulated. In contrast, the lower dose on cells was accurately inferred by the DG model in the case of "non-sticky" boundary conditions. Finally, the presence of cells seemed to enhance particle deposition, as aerial densities on cell-free substrates were clearly reduced. CONCLUSIONS: Our results further validate the use of particokinetic models but also demonstrate their limitations, specifically, with respect to the spatial distribution of particles on heterogeneous surfaces. Consideration of surface properties with respect to adhesion and desorption should advance modelling approaches to ultimately predict the cellular dose with higher precision.

Preparation, Characterization and In Vivo Assessment of Repaglinide Nanosuspension for Oral Bioavailability Improvement.

AIMS AND BACKGROUND: The objective of the study was to improve the bioavailability of poorly soluble repaglinide (RPG) by preparing nanosuspension with poloxamer 188 using high pressure homogenization (HPH). The recent patents on nanocrystals (US20150337006A1) facilitated selection of drug and polymer. METHODS: Suspensions containing dissimilar sized particles were prepared by ultrasonication and HPH. The prepared aqueous suspensions were lyophilized and then characterized. Further, the dried aqueous suspensions were evaluated for drug content, solubility, in vitro dissolution, oral bioavailability study and stability study. RESULTS: RPG nanoparticles size, polydispersity index (PDI) and zeta potential were found to be 280.8 ± 15 nm, 0.279 ± 0.04 and - 25.81 ± 1.6mV, respectively. DSC and XRD results showed that RPG particles in aqueous suspensions were present in a crystalline state; however, RPG nanoparticles exhibited decreased lattice energy due to smaller particle size. Nanoparticles prepared by HPH exhibited significant improvements in solubility and dissolution rate. Oral bioavailability was found to be enhanced by 1.93 fold in comparison with that of plain RPG. The nanosuspension was found to be stable when stored at 5°C ± 3°C. CONCLUSION: The outcomes of the study revealed significant enhancement in dissolution rate and oral bioavailability of RPG due to size reduction to nano range by HPH.

Efficient synthesis of PMMA@Co0.5Ni0.5Fe2O4 organic-inorganic hybrids containing hyamine 1622 - Physicochemical properties, cytotoxic assessment and antimicrobial activity.

The PMMA@Co0.5Ni0.5Fe2O4 ferrite containing hybrid nanomaterials with hyamine were prepared using emulsion polymerization method. Structural and morphological properties were evaluated using XRD, FT-IR, SEM techniques. The TGA and DTA analysis were performed in order to study the thermal properties of hybrid materials in contrast to reference material. Magnetic properties were studied using Quantum Design PPMS (VSM option) in a constant external magnetic field equal (100 Oe and 1000 Oe) in the temperature range from 2 to 380 K. Both the pure Co0.5Ni0.5Fe2O4and the sample with 85% of PMMA exhibit superparamagnetic behavior whereas blocking temperatureTB decreases with increase of PMMA content. The cytotoxicity assessment of PMMA@Co0.5Ni0.5Fe2O4 with hyamine in J774.E murine macrophages and U2OS human osteosarcoma cell lines was performed. Additionally, sensitivity of bacteria Escherichia coli ATCC 8739 and Staphylococcus aureus ATCC 25923 to hybrid materials (with/without hyamine) was investigated using a of Kirby-Bauer disc method.

Rapid identification of regulated organic chemical compounds in toys using ambient ionization and a miniature mass spectrometry system.

Rapid, on-site analysis was achieved through significantly simplified operation procedures for a wide variety of toy samples (crayon, temporary tattoo sticker, finger paint, modeling clay, and bubble solution) using a miniature mass spectrometry system with ambient ionization capability. The labor-intensive analytical protocols involving sample workup and chemical separation, traditionally required for MS-based analysis, were replaced by direct sampling analysis using ambient ionization methods. A Mini ß ion trap miniature mass spectrometer was coupled with versatile ambient ionization methods, e.g. paper spray, extraction spray and slug-flow microextraction nanoESI for direct identification of prohibited colorants, carcinogenic primary aromatic amines, allergenic fragrances, preservatives and plasticizers from raw toy samples. The use of paper substrates coated with Co3O4 nanoparticles allowed a great increase in sensitivity for paper spray. Limits of detection as low as 5µgkg-1 were obtained for target analytes. The methods being developed based on the integration of ambient ionization with miniature mass spectrometer represent alternatives to current in-lab MS analysis operation, and would enable fast, outside-the-lab screening of toy products to ensure children's safety and health.

Biocompatibility assessment of titanium dioxide nanoparticles in mice fetoplacental unit.

As the applications of titanium dioxide nanomaterials (nTiO2 ) are growing with an ever-increasing speed, the hazardous risks of this material have become a major concern. Several recent studies have reported that nTiO2 can cross the placental barrier in pregnant mice and cause neurotoxicity in their offspring. However, the influence of these nanoparticles on the fetoplacental unit during the pregnancy is yet to be studied. The present study reports on the effects of nTiO2 on the anatomical structure of fetal brain and liver in a pregnant mice model. Moreover, changes in the size and weight of the fetus and placenta are investigated as markers of fetal growth. Lastly, the toxicity of nTiO2 in primary brain and liver is quantified. Animals treated with nTiO2 showed a disrupted anatomical structure of the fetal brain and liver. Furthermore, the fetus and placental unit in the mice treated with these nanoparticles were smaller compared to untreated controls. Toxicity analyses revealed that nTiO2 was toxic to the brain and liver cells and the mechanism of cell death was mostly necrosis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 580-589, 2018.

Metal load assessment in patient pulmonary lavages: towards a comprehensive mineralogical analysis including the nano-sized fraction.

Mineralogical analyses of clinical samples have been proved useful to identify causal relationship between exposure to airborne particles and pulmonary diseases. The most striking example is asbestosis where the assessment of asbestos bodies in patient lung samples has allowed defining values specific of pathologies. However, this type of analyses only considers the micro-sized fraction of the particles, neglecting the specific impact of nano-sized particles which have been otherwise shown to be reactive and able to induce biological effects. Similarly, in nanotoxicology, the mineralogical analysis of pulmonary fluids could be used as an indicator of exposure to inhaled nanoparticles and could help investigations on the relationship between exposure to these nanoparticles and lung diseases. We designed this study first to demonstrate the technical feasibility of this approach, then to get a clear picture of the metals present, and in what form, in patient lungs and finally to determine if indeed it is worth investigating separately the micro, sub-micro and nano fractions. Broncho-alveolar lavages were recovered from 100 patients suffering from interstitial lung diseases. A protocol was specifically developed to isolate three fractions containing respectively microparticles, sub-microparticles and nanoparticles with ions. The metal content in each fraction was qualitatively and quantitatively characterized. Results showed significant differences between the three fractions in terms of metal load confirming that the separate analysis of the fractions is relevant. It also means that the assessment of the micro-sized fraction alone, as commonly done in clinical practice, only gives a partial view of the mineralogical analysis.

Assessment of the removal of side nanoparticulated populations generated during one-pot synthesis by asymmetric flow field-flow fractionation coupled to elemental mass spectrometry.

Coupling of asymmetric flow field-flow fractionation (AF4) to an on-line elemental detection (inductively coupled plasma-mass spectrometry, ICP-MS) has been recently proposed as a powerful diagnostic tool for characterization of the bioconjugation of CdSe/ZnS core-shell Quantum Dots (QDs) to antibodies. Such approach has been used herein to demonstrate that cap exchange of the native hydrophobic shell of core/shell QDs with the bidentate dihydrolipoic acid ligands directly removes completely the eventual side nanoparticulated populations generated during simple one-pot synthesis, which can ruin the subsequent final bioapplication. The critical assessment of the chemical and physical purity of the surface-modified QDs achieved allows to explain the transmission electron microscopy findings obtained for the different nanoparticle surface modification assayed.

Assessment of Local Heterogeneity in Mechanical Properties of Nanostructured Hydrogel Networks.

Our current understanding of the mechanical properties of nanostructured biomaterials is rather limited to invasive/destructive and low-throughput techniques such as atomic force microscopy, optical tweezers, and shear rheology. In this report, we demonstrate the capabilities of recently developed dual Brillouin/Raman spectroscopy to interrogate the mechanical and chemical properties of nanostructured hydrogel networks. The results obtained from Brillouin spectroscopy show an excellent correlation with the conventional uniaxial and shear mechanical testing. Moreover, it is confirmed that, unlike the macroscopic conventional mechanical measurement techniques, Brillouin spectroscopy can provide the elasticity characteristic of biomaterials at a mesoscale length, which is remarkably important for understanding complex cell-biomaterial interactions. The proposed technique experimentally demonstrated the capability of studying biomaterials in their natural environment and may facilitate future fabrication and inspection of biomaterials for various biomedical and biotechnological applications.