Azeotropic Distillation-Induced Self-Assembly of Mesostructured Spherical Nanoparticles as Drug Cargos for Controlled Release of Curcumin.

Methods of large-scale controllable production of uniform monodispersed spherical nanoparticles have been one of the research directions of scientists in recent years. In this paper, we report an azeotropic distillation-induced evaporation self-assembly method as a universal method, and monodispersed hydrophobic ordered mesoporous silica nanospheres (MHSs) were successfully synthesized by this method, using triethoxymethylsilane (MTES) as the silica precursor and hexadecyl trimethyl ammonium bromide (CTAB) as the template. SEM and TEM images showed good monodispersity, sphericity, and uniform diameter. Meanwhile, SAXS and N2 adsorption-desorption measurements demonstrated a highly ordered lamellar mesostructure with a large pore volume. The model drug, curcumin was successfully encapsulated in MHSs for drug delivery testing, and their adsorption capacity was 3.45 mg g-1, which greatly improved the stability of curcumin. The release time when net release rate of curcumin reached 50% was extended to 6 days.

One-Spot Facile Synthesis of Single-Crystal LiNi0.5Co0.2Mn0.3O2 Cathode Materials for Li-ion Batteries.

The layered lithium-metal oxides are promising cathode materials for Li-ion batteries. Nevertheless, their widespread applications have been limited by the high cost, complex process, and poor stability resulting from the Ni2+/Li+ mixing. Hence, we have developed a facile one-spot method combining glucose and urea to form a deep eutectic solvent, which could lead to the homogeneous distribution and uniform mixing of transition-metal ions at the atomic level. LiNi0.5Co0.2Mn0.3O2 (NCM523) polyhedron with high homogeneity could be obtained through in situ chelating Ni2+, Co3+, and Mn4+ by the amid groups. The prepared material exhibits a relatively high initial electrochemical property, which is due to the unique single-crystal hierarchical porous nano/microstructure, the polyhedron with exposed active surfaces, and the negligible Ni2+/Li+ mixing level. This one-spot approach could be expanded to manufacture other hybrid transition-metal-based cathode materials for batteries.

A N-doped porous carbon derived from deep eutectic solvent for adsorption of organic contaminants from aqueous or oil solution.

Porous N-doped carbon material (NCM) derived from deep eutectic solvent (DES) is successfully prepared. The preparation of NCM depends mainly on heating treatment and does not demand activation and filtration. The heating process contains three steps: (1) forming a DES that consists of glucose and urea at 100 °C; (2) preparing dried precursors by microwave; (3) and carbonizing the precursor. After heating, the resulting NCM can be obtained. The as-prepared NCM exhibits high specific surface area, rich micropores and strong Lewis basicity. Accordingly, NCMs show good adsorption performance for 4-nitrophenol or methylene blue in aqueous solution and thiophenic sulfurs in the oil phase. Apparently, NCM derived from DES not only possesses a simple preparation process, but also can remove a wide spectrum of organic pollutants. Therefore, the NCM prepared here may be promising for practical application.

High Catalytic Performance of Mn-Doped Ce-Zr Catalysts for Chlorobenzene Elimination.

Mn-Ce-Zr-O catalysts doped with varying Mn content were prepared and assessed for the catalytic combustion of chlorobenzene (CB). Nanosized MCZ-0.67 catalyst with amorphous phase exhibited a high and stable catalytic activity among the studied catalysts, achieving 90% CB conversion at 226 °C and withstanding stability tests, including time-based stability and the successive influence of various operating conditions. Meanwhile, the MCZ-0.67 catalyst used showed good recyclability by calcination in air. Characterization results suggested that Mn doping played a dominant role in improving the catalytic performance, resulting in larger surface area, better redox properties and greater amounts of surface active oxygen. In addition, the introduction of Zr was also indispensable for maintaining the good catalytic performance of catalysts. Finally, trace amounts of polychlorinated by-products during CB oxidation were monitored and the oxidation process was discussed.

The Possible Mechanisms of HSV-TK/Hyperthermia Combined with 131I-antiAFPMcAb-GCV Nanospheres to Treat Hepatoma.

Our previous findings showed a good therapeutic effect of the combination of suicide gene HSV-TK, nuclide 131I, and magnetic fluid hyperthermia (MFH) on hepatoma by using magnetic nanoparticles as linkers, far better than any monotherapy involved, with no adverse effects. This combination therapy might be an eligible strategy to treat hepatic cancer. However, it is not clear how the combination regimen took the therapeutic effects. In the current study, to explore the possible mechanisms of radionuclide-gene therapy combined with MFH to treat hepatoma at tissue, cellular, and molecular levels and to provide theoretical and experimental data for its clinical application, we examined the apoptosis induction of the combination therapy and investigated the expression of the proteins related to apoptosis such as survivin, livin, bcl-2, p53, and nucleus protein Ki67 involved in cell proliferation, detected VEGF, and MVD involved in angiogenesis of tumor tissues and analyzed the pathologic changes after treatment. The results showed that the combination therapy significantly induced the hepatoma cell apoptosis. The expression of survivin, VEGF, bcl-2, p53, livin, Ki67, and VEGF proteins and microvascular density (MVD) were all decreased after treatment. The therapeutic mechanisms may be involved in the downregulation of Ki67 expression leading to tumor cell proliferation repression and inhibition of survivin, bcl-2, p53, and livin protein expression inducing tumor cell apoptosis, negatively regulating VEGF protein expression, and reducing vascular endothelial cells, which results in tumor angiogenesis inhibition and microvascular density decrease and tumor cell necrosis. These findings offer another basic data support and theoretical foundation for the clinical application of the combination therapy.

The Recent Advances on Liver Cancer Stem Cells: Biomarkers, Separation, and Therapy.

As the third major reason of mortality related to cancer in the world, liver cancer is also the fifth most frequent cancer. Unluckily, a majority of patients succumb and relapse though many progresses have been made in detection and therapy of liver cancer. It has been put forward that in liver cancer, cancer stem cells (CSCs) hold main responsibility for the formation, invasion, metastasis, and recurrence of tumor. Strategies that are intended to target liver CSCs are playing a more and more significant role in supervising the development of liver cancer treatment and assessing new therapeutic methods. Herein, a brief review about molecule markers, signal pathways, separation, and treatment on liver cancer stem cells (LCSCs) is provided in this paper.

[Influence of Fe 2O 3 nanoparticles on the rhological properties of simulated asthma airway mucus].

The properties of mucus in a person with asthma can alter with disease process so that it may lead to the airway embolism. Fe 2O 3 nanoparticles can be used for drug delivery. Up till now, however, little is known about how the Fe 2O 3 nanoparticles influence the properties of airway mucus. In this study, Fe 2O 3 nanoparticles were dispersed with ultrasound, and the morphological properties were measured with scanning electron microscope, atomic force microscope and nanometer laser particle size and zeta potential analyzer. Then the dispersed Fe 2O 3 nanoparticles were added to the simulated asthma airway mucus with different final concentration (0.03, 0.3, and 0.4 mg/mL). The measurements of flow curve, yield stress, large amplitude oscillatory shear (LAOS) and shock scanning were carried out with a rotational rheometer. Experimental results showed that the Fe 2O 3 nanoparticles reduced the zero shear viscosity of simulated asthma airway mucus. With increase of shear rate, the wind speed of mucus was reduced. The yield stress of simulated asthma airway mucus was 19.0 Pa, but the yield stresses of experimental group (0.03, 0.3 and 0.4 mg/mL) were 17.0, 0.99, and 0.7 Pa, respectively. The results showed that the viscoelastic modulus of asthma airway mucus treated with Fe 2O 3 nanoparticles were changed obviously as measured with large amplitude scanning and frequency scanning. By adopting the method of optical phase microscopy, we found that different structures of simulated airway mucus were absorbed. The results showed Fe 2O 3 nanoparticles distroyed mucus structure. The experimental results proved that Fe 2O 3 nanoparticles could change the rheological characteristics of simulated asthma airway mucus. This experimental result would lay a foundation for the further development of airway mucus sticky agent based on the function of Fe 2O 3 nanoparticles.

A combination hepatoma-targeted therapy based on nanotechnology: pHRE-Egr1-HSV-TK/(131)I-antiAFPMcAb-GCV/MFH.

Combination targeted therapy is a promising cancer therapeutic strategy. Here, using PEI-Mn0.5Zn0.5Fe2O4 nanoparticles (PEI-MZF-NPs) as magnetic media for MFH (magnetic fluid hyperthermia) and gene transfer vector for gene-therapy, a combined therapy, pHRE-Egr1-HSV-TK/(131)I-antiAFPMcAb-GCV/MFH, for hepatoma is developed. AntiAFPMcAb (Monoclonal antibody AFP) is exploited for targeting. The plasmids pHRE-Egr1-HSV-TK are achieved by incorporation of pEgr1-HSV-TK and pHRE-Egr1-EGFP. Restriction enzyme digestion and PCR confirm the recombinant plasmids pHRE-Egr1-HSV-TK are successfully constructed. After exposure to the magnetic field, PEI-MZF-NPs/pHRE-Egr1-EGFP fluid is warmed rapidly and then the temperature is maintained at 43 °C or so, which is quite appropriate for cancer treatment. The gene expression reaches the peak when treated with 200 µCi (131)I for 24 hours, indicating that the dose of 200 µCi might be the optimal dose for irradiation and 24 h irradiation later is the best time to initiate MFH. The in vitro and in vivo experiments demonstrate that pHRE-Egr1-HSV-TK/(131)I-antiAFPMcAb-GCV/MFH can greatly suppress hepatic tumor cell proliferation and induce cell apoptosis and necrosis and effectively inhibit the tumor growth, much better than any monotherapy does alone. Furthermore, the combination therapy has few or no adverse effects. It might be applicable as a strategy to treat hepatic cancer.

Hepatoma-Targeted Radionuclide Immune Albumin Nanospheres: (131)I-antiAFPMcAb-GCV-BSA-NPs.

An effective strategy has been developed for synthesis of radionuclide immune albumin nanospheres ((131)I-antiAFPMcAb-GCV-BSA-NPs). In vitro as well as in vivo targeting of (131)I-antiAFPMcAb-GCV-BSA-NPs to AFP-positive hepatoma was examined. In cultured HepG2 cells, the uptake and retention rates of (131)I-antiAFPMcAb-GCV-BSA-NPs were remarkably higher than those of (131)I alone. As well, the uptake rate and retention ratios of (131)I-antiAFPMcAb-GCV-BSA-NPs in AFP-positive HepG2 cells were also significantly higher than those in AFP-negative HEK293 cells. Compared to (131)I alone, (131)I-antiAFPMcAb-GCV-BSA-NPs were much more easily taken in and retained by hepatoma tissue, with a much higher T/NT. Due to good drug-loading, high encapsulation ratio, and highly selective affinity for AFP-positive tumors, the (131)I-antiAFPMcAb-GCV-BSA-NPs are promising for further effective radiation-gene therapy of hepatoma.

Azeotropic distillation assisted fabrication of silver nanocages and their catalytic property for reduction of 4-nitrophenol.

Monodisperse silver nanocages (AgNCs) with specific interiors were successfully synthesized by an azeotropic distillation (AD) assisted method and exhibited excellent catalytic activities for reduction of 4-nitrophenol (4-NP) into 4-aminophenol (4-AP) due to the unique hollow morphology and small thickness of the silver shell.

Influence of material properties on TiO2 nanoparticle agglomeration.

Emerging nanomaterials are being manufactured with varying particle sizes, morphologies, and crystal structures in the pursuit of achieving outstanding functional properties. These variations in these key material properties of nanoparticles may affect their environmental fate and transport. To date, few studies have investigated this important aspect of nanoparticles' environmental behavior. In this study, the aggregation kinetics of ten different TiO2 nanoparticles (5 anatase and 5 rutile each with varying size) was systematically evaluated. Our results show that, as particle size increases, the surface charge of both anatase and rutile TiO2 nanoparticles shifts toward a more negative value, and, accordingly, the point of zero charge shifts toward a lower value. The colloidal stability of anatase sphere samples agreed well with DLVO theoretical predictions, where an increase in particle size led to a higher energy barrier and therefore greater critical coagulation concentration. In contrast, the critical coagulation concentration of rutile rod samples correlated positively with the specific surface area, i.e., samples with higher specific surface area exhibited higher stability. Finally, due to the large innate negative surface charge of all the TiO2 samples at the pH value (pH = 8) tested, the addition of natural organic matter was observed to have minimal effect on TiO2 aggregation kinetics, except for the smallest rutile rods that showed decreased stability in the presence of natural organic matter.

Mesoporous silica-supported lipid bilayers (protocells) for DNA cargo delivery to the spinal cord.

Amorphous mesoporous silica nanoparticles ('protocells') that support surface lipid bilayers recently characterized in vitro as carrier constructs for small drug and DNA delivery are reported here as highly biocompatible both in vitro and in vivo, involving the brain and spinal cord following spinal delivery into the lumbosacral subarachnoid space (intrathecal; i.t.). Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP)-cholesterol (DOTAP:Chol) liposome-formulated protocells revealed stable in vitro cargo release kinetics and cellular interleukin-10 (IL-10) transgene transfection. Recent approaches using synthetic non-viral vector platforms to deliver the pain-suppressive therapeutic transgene, IL-10, to the spinal subarachnoid space have yielded promising results in animal models of peripheral neuropathy, a condition involving aberrant neuronal communication within sensory pathways in the nervous system. Non-viral drug and gene delivery protocell platforms offer potential flexibility because cargo release-rates can be pH-dependent. We report here that i.t. delivery of protocells, with modified chemistry supporting a surface coating of DOTAP:Chol liposomes and containing the IL-10 transgene, results in functional suppression of pain-related behavior in rats for extended periods. This study is the first demonstration that protocell vectors offer amenable and enduring in vivo biological characteristics that can be applied to spinal gene delivery.

Processing pathway dependence of amorphous silica nanoparticle toxicity: colloidal vs pyrolytic.

We have developed structure/toxicity relationships for amorphous silica nanoparticles (NPs) synthesized through low-temperature colloidal (e.g., Stöber silica) or high-temperature pyrolysis (e.g., fumed silica) routes. Through combined spectroscopic and physical analyses, we have determined the state of aggregation, hydroxyl concentration, relative proportion of strained and unstrained siloxane rings, and potential to generate hydroxyl radicals for Stöber and fumed silica NPs with comparable primary particle sizes (16 nm in diameter). On the basis of erythrocyte hemolytic assays and assessment of the viability and ATP levels in epithelial and macrophage cells, we discovered for fumed silica an important toxicity relationship to postsynthesis thermal annealing or environmental exposure, whereas colloidal silicas were essentially nontoxic under identical treatment conditions. Specifically, we find for fumed silica a positive correlation of toxicity with hydroxyl concentration and its potential to generate reactive oxygen species (ROS) and cause red blood cell hemolysis. We propose fumed silica toxicity stems from its intrinsic population of strained three-membered rings (3MRs) along with its chainlike aggregation and hydroxyl content. Hydrogen-bonding and electrostatic interactions of the silanol surfaces of fumed silica aggregates with the extracellular plasma membrane cause membrane perturbations sensed by the Nalp3 inflammasome, whose subsequent activation leads to secretion of the cytokine IL-1ß. Hydroxyl radicals generated by the strained 3MRs in fumed silica, but largely absent in colloidal silicas, may contribute to the inflammasome activation. Formation of colloidal silica into aggregates mimicking those of fumed silica had no effect on cell viability or hemolysis. This study emphasizes that not all amorphous silicas are created equal and that the unusual toxicity of fumed silica compared to that of colloidal silica derives from its framework and surface chemistry along with its fused chainlike morphology established by high-temperature synthesis (>1300 °C) and rapid thermal quenching.

Aerosol-assisted synthesis of monodisperse single-crystalline α-cristobalite nanospheres.

Monodisperse single-crystalline α-cristobalite nanospheres have been synthesized by hydrocarbon-pyrolysis-induced carbon deposition on amorphous silica aerosol nanoparticles, devitrification of the coated silica at high temperature, and subsequent carbon removal by oxidation. The nanosphere size can be well controlled by tuning the size of the colloidal silica precursor. Uniform, high-purity nanocrystalline α-cristobalite is important for catalysis, nanocomposites, advanced polishing, and understanding silica nanotoxicology.

Hydrothermal synthesis of monodisperse single-crystalline alpha-quartz nanospheres.

Uniformly-sized, single-crystal alpha-quartz nanospheres have been synthesized at 200 °C and 15 atm under continuous stirring starting from uniform, amorphous Stöber silica colloids and using NaCl and alkali hydroxide as mineralizers. Quartz nanosphere size is controlled by the colloid particle size via direct devitrification. Uniform, high-purity nanocrystalline quartz is important for understanding nanoparticle toxicology and for advanced polishing and nanocomposite fabrication.

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes.

Rigid templating of high surface-area, mesoporous, nanocrystalline rutile using a polyether block amide copolymer template.

Highly crystalline rutile with a specific surface area as high as 280 m(2) g(-1) and well-connected uniform mesoporosity has been synthesized by rigid templating using commercial, low-cost polyether block amide. This general, simple synthesis route for high surface-area mesoporous nanocrystalline oxides and nanocomposite membranes is important for catalysis, sensors, energy storage, solar cells, heavy metal removal and separations.

Aerosol fabrication of hollow mesoporous silica nanoparticles and encapsulation of L-methionine as a candidate drug cargo.

Hollow spherical nanoparticles with ordered mesoporous silica shells were fabricated by evaporation-induced self-assembly using (NH(4))(2)SO(4) and cetyltrimethyl ammonium bromide (CTAB) as templates. The model drug, L-methionine, was encapsulated within the spherical void at high loadings by repeated crystallization.

Measurements and simulations of the near-surface composition of evaporating ethanol-water droplets.

The evolving composition of evaporating ethanol-water droplets (initially 32.6 or 45.3 microm radius) is probed by stimulated Raman scattering over the period 0.2 to 3 ms following droplet generation and with a surrounding nitrogen gas pressure in the range 10 to 100 kPa. The dependence of the evaporation rate on the relative humidity of the surrounding gas phase is also reported. The measured data are compared with both a quasi-steady state model and with numerical simulations of the evaporation process. Results from the numerical simulations are shown to agree closely with the measurements when the stimulated signal is assumed to arise from an outer shell with a probe depth of 2.9+/-0.4% of the droplet radius, consistent with a previous determination. Further, the time-dependent measurements are shown to be sensitive to the development of concentration gradients within evaporating droplets. This represents the first direct measurement of the spatial gradients in composition that arise during the evaporation of aerosol droplets and allows the influence of liquid phase diffusion within the condensed phase on droplet evaporation to be examined.

Electrostatically mediated liposome fusion and lipid exchange with a nanoparticle-supported bilayer for control of surface charge, drug containment, and delivery.

The loading and containment of cargo within nanoparticles and their efficient delivery to cells represent a primary challenge in nanomedicine. We report lipid exchange between free and mesoporous silica nanoparticle-supported lipid bilayers as an effective means of containing cargo, controlling charge, and directing delivery to mammalian cells. The delivery of a membrane-impermeable dye (calcein) and a chemotherapeutic drug (doxorubicin) are demonstrated. Exchanged lipid bilayers minimized premature drug release, and an overall positive charge on the supported lipid bilayer effected enhanced delivery.