Self-assembly of highly symmetrical, ultrasmall inorganic cages directed by surfactant micelles.

Nanometre-sized objects with highly symmetrical, cage-like polyhedral shapes, often with icosahedral symmetry, have recently been assembled from DNA1-3, RNA 4 or proteins5,6 for applications in biology and medicine. These achievements relied on advances in the development of programmable self-assembling biological materials7-10, and on rapidly developing techniques for generating three-dimensional (3D) reconstructions from cryo-electron microscopy images of single particles, which provide high-resolution structural characterization of biological complexes11-13. Such single-particle 3D reconstruction approaches have not yet been successfully applied to the identification of synthetic inorganic nanomaterials with highly symmetrical cage-like shapes. Here, however, using a combination of cryo-electron microscopy and single-particle 3D reconstruction, we suggest the existence of isolated ultrasmall (less than 10 nm) silica cages ('silicages') with dodecahedral structure. We propose that such highly symmetrical, self-assembled cages form through the arrangement of primary silica clusters in aqueous solutions on the surface of oppositely charged surfactant micelles. This discovery paves the way for nanoscale cages made from silica and other inorganic materials to be used as building blocks for a wide range of advanced functional-materials applications.

Anchoring of a hydrophobic heptapeptide (AFILPTG) on silica facilitates peptide unfolding at the abiotic-biotic interface.

A hydrophobic heptapeptide, with sequence AFILPTG, as part of a phage capsid protein binds effectively to silica particles carrying negative charge. Here, we explore the silica binding activity of the sequence as a short polypeptide with polar N and C terminals. To describe the structural changes that occur on binding, we fit experimental infrared, Raman and circular dichroism data for a number of structures simulated in the full configuration space of the hepta-peptide using replica exchange molecular dynamics. Quantum chemistry was used to compute normal modes of infrared and Raman spectra and establish a relationship to structures from MD data. To interpret the circular dichroism data, instead of empirical factoring of optical activity into helical/sheet/random components, we exploit natural transition orbital theory and specify the contributions of backbone amide units, side chain functional groups, water, sodium ions and silica to the observed transitions. Computed optical responses suggest a less folded backbone and importance of the N-terminal when close to silica. We further discuss the thermodynamics of the interplay of charged and hydrophobic moieties of the polypeptide on association with the silica surface. The outcomes of this study may assist in the engineering of novel artificial bio-silica heterostructures.

Synthesis of Vertically Aligned Porous Silica Thin Films Functionalized by Silver Ions.

In this work, we have developed a chemical procedure enabling the preparation of highly ordered and vertically aligned mesoporous silica films containing selected contents of silver ions bonded inside the mesopore channels via anchoring propyl-carboxyl units. The procedure involves the electrochemically assisted self-assembly co-condensation of tetraethoxysilane and (3-cyanopropyl)triethoxysilane in the presence of cetyltrimethylammonium bromide as a surfactant, the subsequent hydrolysis of cyano groups into carboxylate ones, followed by their complexation with silver ions. The output materials have been electrochemically characterized with regard to the synthesis effectiveness in order to confirm and quantify the presence of the silver ions in the material. The mesostructure has been observed by transmission electron microscopy. We have pointed out that it is possible to finely tune the functionalization level by controlling the co-condensation procedure, notably the concentration of (3-cyanopropyl)triethoxysilane in the synthesis medium.

Determination of Two Differently Manufactured Silicon Dioxide Nanoparticles by Cloud Point Extraction Approach in Intestinal Cells, Intestinal Barriers and Tissues.

Food additive amorphous silicon dioxide (SiO2) particles are manufactured by two different methods-precipitated and fumed procedures-which can induce different physicochemical properties and biological fates. In this study, precipitated and fumed SiO2 particles were characterized in terms of constituent particle size, hydrodynamic diameter, zeta potential, surface area, and solubility. Their fates in intestinal cells, intestinal barriers, and tissues after oral administration in rats were determined by optimizing Triton X-114-based cloud point extraction (CPE). The results demonstrate that the constituent particle sizes of precipitated and fumed SiO2 particles were similar, but their aggregate states differed from biofluid types, which also affect dissolution properties. Significantly higher cellular uptake, intestinal transport amount, and tissue accumulation of precipitated SiO2 than of fumed SiO2 was found. The intracellular fates of both types of particles in intestinal cells were primarily particle forms, but slowly decomposed into ions during intestinal transport and after distribution in the liver, and completely dissolved in the bloodstream and kidneys. These findings will provide crucial information for understanding and predicting the potential toxicity of food additive SiO2 after oral intake.

Synthesis and Characterization of ZnO-SiO2 Composite Using Oil Palm Empty Fruit Bunch as a Potential Silica Source.

In this paper, the structural and optical properties of ZnO-SiO2-based ceramics fabricated from oil palm empty fruit bunch (OPEFB) were investigated. The OPEFB waste was burned at 600, 700 and 800 °C to form palm ash and was then treated with sulfuric acid to extract silica from the ash. X-ray fluorescence (XRF) and X-ray diffraction (XRD) analyses confirmed the existence of SiO2 in the sample. Field emission scanning electron microscopy (FESEM) showed that the particles displayed an irregular shape and became finer after leaching. Then, the solid-state method was used to produce the ZnO-SiO2 composite and the samples were sintered at 600, 800, 1000, 1200 and 1400 °C. The XRD peaks of the Zn2SiO4 showed high intensity, which indicated high crystallinity of the composite. FESEM images proved that the grain boundaries were larger as the temperature increased. Upon obtaining the absorbance spectrum from ultraviolet-visible (UV-Vis) spectroscopy, the energy band gaps obtained were 3.192, 3.202 and 3.214 eV at room temperature, 600 and 800 °C, respectively, and decreased to 3.127, 2.854 and 2.609 eV at 1000, 1200 and 1400 °C, respectively. OPEFB shows high potential as a silica source in producing promising optical materials.

Quantitative Cooperative Binding Model for Intrinsically Disordered Proteins Interacting with Nanomaterials.

Intrinsically disordered proteins (IDPs) can display a broad spectrum of binding modes and highly variable binding affinities when interacting with both biological and nonbiological materials. A quantitative model of such behavior is important for the better understanding of the function of IDPs when encountering inorganic nanomaterials with the potential to control their behavior in vivo and in vitro. Depending on their amino acid composition and chain length, binding properties can vary strongly between different IDPs. Moreover, due to differences in the physical chemical properties of clusters of amino acid residues along the IDP primary sequence, individual residues can adopt a wide range of bound state populations. Quantitative experimental binding affinities with synthetic silica nanoparticles (SNPs) at residue-level resolution, which were obtained for a set of IDPs by solution NMR relaxation experiments, are explained here by a first-principle analytical statistical mechanical model termed SILC. SILC quantitatively predicts residue-specific binding affinities to nanoparticles and it expresses binding cooperativity as the cumulative result of pairwise residue effects. The model, which was parametrized for anionic SNPs and applied to experimental data of four IDP systems with distinctive binding behavior, successfully predicts differences in overall binding affinities, fine details of IDP-SNP affinity profiles, and site-directed mutagenesis effects with a spatial resolution at the individual residue level. The SILC model provides an analytical description of such types of fuzzy IDP-SNP complexes and may help advance understanding nanotoxicity and in vivo targeting of IDPs by specifically designed nanomaterials.

Aminophenylboronic Acid-Functionalized Thorny-Trap-Shaped Monolayer Microarray for Efficient Capture and Release of Circulating Tumor Cells.

An aminophenylboronic acid (APBA)-functionalized thorny-trap-shaped monolayer microarray as a 3D fractal structures' substrate was fabricated to capture and release circulating tumor cells (CTCs) efficiently. The microarray can not only trap cells inside by microbowls but also enhance the interaction between cell and substrate by providing more binding sites and facilitating the spread of cell filopodias via the growth of nanorods. Modification of APBA enhanced the interaction further by binding with sialic acid of CTCs surface. The special topological structure achieved a high capture efficiency of 79.5%. The captured cancer cells were released without introducing any affinity molecules by a ligand exchange reaction with up to 70% efficiency and good proliferation. This substrate can isolate 33 tumor cells from a mimic blood sample even at a low spiked number of 50 cancer cells. This study provides valuable guidance for isolation and release of CTCs and is significant for the further study of tumors.

Fabrication and investigation of gold (III) ion-imprinted functionalized silica particles.

Au (III) ion-imprinted mesoporous silica particles (Au-Si-Py) was manufactured by the condensation reaction of (3-Aminopropyl)triethoxysilane (AT)and 2-pyridinecarboxaldehyde (Py). The obtained AT-Py Schiff base ligand was then coordinate with the template gold ions and the polymerizable gold-complex was allowed to gel in presence of tetraethoxysilane (TEOS) and then the coordinated gold ions were leached out of the obtained silica matrix using acidified thiourea solution. During the synthetic steps, the obtained materials were investigated utilizing advanced instrumental and spectral methods. Moreover, the morphological structure of both Au (III) ions imprinted Au-Si-Py and non-imprinted NI-Si-Py silica particles were visualized using scanning electron microscope (SEM). Various adsorption experiments had been carried out using both Au-Si-Py and NI-Si-Py to examine their potential for selective extraction of gold ions under different conditions.

Multifunctional ZnO/SiO2 Core/Shell Nanoparticles for Bioimaging and Drug Delivery Application.

Semiconducting nanoparticles with luminescent properties are used as detection probes and drug carriers in in-vitro and in-vivo analysis. ZnO nanoparticles, due to its biocompatibility and low cost, have shown potential application in bioimaging and drug delivery. Thus, ZnO/SiO2 core/shell nanoparticle was synthesised by wet chemical method for fluorescent probing and drug delivery application. The synthesised core/shell nanomaterial was characterized using XRD, FTIR, UV-VIS spectroscopy, Raman spectroscopy, TEM and PL analysis. The silicon shell enhances the photoluminescence and aqueous stability of the pure ZnO nanoparticles. The porous surface of the shell acts as a carrier for sustained release of curcumin. The synthesized core/shell particle shows high cell viability, hemocompatibility and promising florescent property. Graphical Abstract.

Preparation of Boronic Acid-Functionalized Silica Nanocomposites for Selective Enrichment of Glycoproteins.

A facile method was developed for synthesis of boronic acid-functionalized silica nanocomposites (SiO2 -BA) by 'thiol-ene' click reaction, where silica nanoparticles were synthesized by using tetraethoxysilane (TEOS) and γ-mercaptopropyl trimethoxysilane (γ-MPTS) as precursors. The morphology and structure properties of the resultant SiO2 -BA were characterized by transmission electronic microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and Brunner-Emmet-Teller measurements (BET). The adsorption behavior of the SiO2 -BA for glycoproteins was evaluated. Under the optimized conditions, the SiO2 -BA exhibited higher adsorption capacity towards glycoproteins (ovalbumin, OVA, 7.64 µmol/g) than non-glycoproteins (bovine serum albumin, BSA, 0.83 µmol/g). In addition, the practicality of the SiO2 -BA was further assessed by selective enrichment of glycoproteins from egg white samples.

Synthesis of fully porous silica microspheres with high specific surface area for fast HPLC separation of intact proteins and digests of ovalbumin.

Fully porous silica microspheres (FPSM) with high specific surface area and hierarchical pore as matrix for HPLC were prepared. First, the porous silica nanospheres with controllable particle size and pore diameter were successfully synthesized using a dual-templating approach, the pore size of nanospheres can be increased to 18.4 nm by changing the molar ratios of octyltrimethylammonium bromide (TOMAB) and cetyltrimethyl ammonium bromide (CTAB), which is suitable for separation and analysis of biomolecules without pore enlargement. Then, the micron FPSM with hierarchical pore were synthesized by polymerization-induced colloid aggregation (PICA) using the porous nanospheres as a silicon source, which has a large mesoporous structure (35.2 nm) and high specific surface area (560 m2 g-1). Subsequently, the FPSM modified with octadecyltrichlorosilane were studied as stationary phase for separation of cytochrome C, lysozyme, ribonuclease A, and ovalbumin, bovine serum albumin, and the baseline separation of five proteins was achieved within 1 min. The prepared column was also applied to the fast separation of digests of ovalbumin, and more chromatographic peaks were obtained compared to a commercial column under the same gradient elution conditions. In addition, the static-binding capacity of the functionalized FPSM for bovine serum albumin (BSA) was measured to be 276 mg g-1, which was nearly twice the static adsorption given in literature. Therefore, these FPSM with high specific surface area and hierarchical pore structure are expected to have great potential for the separation of complex biological samples using HPLC. Graphical abstract A synthetic strategy was provided towards FPSM with hierarchical pores and high specific surface area using porous nanospheres as silicon source. The outstanding performance of the FPSM is that it has a high specific surface area while maintaining a large mesoporous size, which overcomes the disadvantage of sacrificing the specific surface area when increasing the pore size of porous silica microspheres prepared by using the traditional PICA method.

Production of MCM-41 Nanoparticles with Control of Particle Size and Structural Properties: Optimizing Operational Conditions during Scale-Up.

The synthesis of Mobil Composition of Matter 41 (MCM-41) mesoporous silica nanoparticles (MSNs) of controlled sizes and porous structure has been performed at laboratory and pilot plant scales. Firstly, the effects of the main operating conditions (TEOS -Tetraethyl ortosilicate- addition rate, nanoparticle maturation time, temperature, and CTAB -Cetrimonium bromide- concentration) on the synthesis at laboratory scale (1 L round-bottom flask) were studied via a Taguchi experimental design. Subsequently, a profound one-by-one study of operating conditions was permitted to upscale the process without significant particle enlargement and pore deformation. To achieve this, the temperature was set to 60 °C and the CTAB to TEOS molar ratio to 8. The final runs were performed at pilot plant scale (5 L cylindrical reactor with temperature and stirring speed control) to analyze stirring speed, type of impeller, TEOS addition rate, and nanoparticle maturation time effects, confirming results at laboratory scale. Despite slight variations on the morphology of the nanoparticles, this methodology provided MSNs with adequate sizes and porosities for biomedical applications, regardless of the reactor/scale. The process was shown to be robust and reproducible using mild synthesis conditions (2 mL⋅min-1 TEOS addition rate, 400 rpm stirred by a Rushton turbine, 60 min maturation time, 60 °C, 2 g⋅L-1 CTAB, molar ratio TEOS/CTAB = 8), providing ca. 13 g of prismatic short mesoporous 100-200 nm nanorods with non-connected 3 nm parallel mesopores.

Controlling Particle Morphology and Pore Size in the Synthesis of Ordered Mesoporous Materials.

Ordered mesoporous materials have attracted considerable attention due to their potential applications in catalysis, adsorption, and separation technologies, as well as biomedical applications. In the present manuscript, we aim at a rational design to obtain the desired surface functionality (Ti and/or hydrophobic groups) while obtaining short channels (short diffusion paths) and large pore size (>10 nm). Santa Barbara Amorphous material SBA-15 and periodic mesoporous organosilica PMO materials are synthesized using Pluronic PE 10400 (P104) surfactant under mild acidic conditions to obtain hexagonal platelet-like particles with very short mesochannels (300-450 nm). The use of expanders, such as 1, 3, 5-trimethylbenzene (TMB) and 1, 3, 5-triisopropylbenzene (TIPB) were tested in order to increase the pore size. TMB yielded in the formation of vesicles in all the syntheses attempted, whereas P104 combined with TIPB resulted both in expanded (E) E-SBA-15 and E-PMO with 12.3 nm pore size short channel particles in both cases. Furthermore, the synthesis method was expanded to the incorporation of small amount of Ti via co-condensation method using titanocene as titanium source. As a result, Ti-E-SBA-15 was obtained with 15.5 nm pore size and isolated Ti-sites maintaining platelet hexagonal morphology. Ti-PMO was obtained with 7.8 nm and short channels, although the pore size under the tried synthesis conditions could not be expanded further without losing the structural ordering.

Ratiometric Fluorescent Quantification of the Size-Dependent Cellular Toxicity of Silica Nanoparticles.

Nanoscale particles are ubiquitous in the atmosphere, and the widespread use of nanoparticles may increase the risks of organ damage. Therefore, it is of great significance to investigate the toxicity of nanoparticles of different sizes toward living cells, especially lung epithelial cells. In this study, the quantitative ratiometric fluorescent detection of intracellular pH changes was utilized to evaluate the cytotoxicity of mesoporous silica nanoparticles of different sizes after the nanoparticles had entered lung epithelial cells. The results showed that, with decreasing nanoparticle size, the intracellular reactive oxygen species (ROS) concentration increased and the intracellular pH value decreased; consequently, this led to the enhanced cytotoxicity of the nanoparticles. Notably, no obvious cytotoxicity was induced by the nanoparticles when the size of the nanoparticles was larger than 135 nm. The presented strategy of using ratiometric fluorescent detection of intracellular pH to quantify the size-dependent cellular toxicity of nanoparticles provides a novel approach for investigating the cytotoxicity of nanomaterials.

Surface Modification of Stöber Silica Nanoparticles with Controlled Moiety Densities Determines Their Cytotoxicity Profiles in Macrophages.

Physicochemical properties of nanomaterials play important roles in determining their toxicological profiles during nano-biointeraction. Among them, surface modification is one of the most effective manners to tune the cytotoxicity induced by nanomaterials. However, currently, there is no consistency in surface modification including moiety types and quantities considering the conflicting toxicological profiles of particles across different studies. In this study, in order to systematically investigate how the moiety density affects cytotoxicity of NPs, we chose three different types of functional groups, that is, -NH2, -COOH, and -PEG, and further controlled their densities on modified Stöber silica nanoparticles (NPs). We demonstrated that densities of functional groups could significantly affect the cytotoxicities of Stöber silica NPs. Regardless of the types of functional groups, high grafting densities could ameliorate the cytotoxicities induced by Stöber silica NPs in macrophages, for example, J774A.1 and N9 cells. When equal amounts of functional groups were present, the cell viability increased in the order of -COOH < -NH2 < -PEG. Furthermore, it was shown that surface modification could significantly affect the quantities of the surface silanol, which is the determining factor that affects their cytotoxicity. These results show that it is critical to control the surface moiety both quantitatively and qualitatively, which can tune the interaction outcomes at the nano-bio interface. The results found in this article provide useful guidance to adjust nanomaterial cytotoxicity for safer biomedical applications.

An optimized mixed-mode stationary phase based on silica monolith particles for the separation of peptides and proteins in high-performance liquid chromatography.

A phase with both hydrophobic and hydrophilic functionalities has been synthesized by modification of ground silica monolith particles with C18 and 1-[3-(trimethoxysilyl)propyl] urea ligands. A series of phases was prepared by changing the ratio of the two ligands to determine the optimal ratio in view of separation efficiency. The resultant optimized stationary phase was packed in narrow-bore glass-lined stainless-steel columns (1 × 300 mm and 2.1 × 100 mm) and used for the separation of synthetic peptides and proteins. The average numbers of theoretical plates (N) of 52 100/column (174 000/m, 5.75 µm plate height) and 35 500/column (118 000/m, 8.47 µm plate height) were achieved with the 300 mm column at a flow rate of 25 µL/min (0.86 mm/s) in 60:40 v/v acetonitrile/30 mM aqueous ammonium formate for the mixture of peptides (Thr-Tyr-Ser, Val-Ala-Pro-Gly, angiotensin I, isotocin, and bradykinin) and for the mixture of proteins (myoglobin, human serum albumin, and insulin), respectively. Fast analysis of the peptides and proteins was also carried out at a flow rate of 0.9 mL/min (6.88 mm/s) with the 100 mm column and all the analytes were eluted within 2 min with good separation efficiency.

Identification of ligands from natural products as inhibitors of glutathione S-transferases using enzyme immobilized mesoporous magnetic beads with high-performance liquid chromatography plus quadrupole time-of-flight mass spectrometry and molecular docking.

Multidrug resistance is recognized as one of the main reasons leading to the failure of chemotherapy. Studies have shown that glutathione S-transferase inhibitors could be regarded as multidrug resistance reversal agents. Herein, a method of applying enzyme immobilization, molecular docking, and high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was employed to screen glutathione S-transferase inhibitors from natural products. Magnetic mesoporous silica microspheres were synthesized and modified with a poly(dopamine) layer, which has a large quantity of amino, enabling further non-covalent binding with glutathione S-transferase. Moreover, the immobilization conditions, namely, potential of hydrogen, catalase concentration, reaction temperature and reaction time, were optimized. In total, six potential compounds were isolated and identified from Perilla frutescens (L.) Britt leaves and green tea and molecular docking was applied to identify the binding site. Rosmarinic acid, (-)-epigallocatechin-3-O-gallate and (-)-epicatechin-3-gallate showed higher binding affinity than the compounds, and their half maximal inhibitory concentration values were further determined. The results suggested that this proposed method was effective and convenient for identifying glutathione S-transferase inhibitors from natural products.

ZnO:SBA-15 Nanocomposites for Potential Use in Sunscreen: Preparation, Properties, Human Skin Penetration and Toxicity.

AIM: We evaluated the effects of the incorporation of zinc oxide (ZnO) nanoparticles in a mesoporous matrix, aiming to improve the textural, structural and morphological properties and verify their safety so that they can be applied in sunscreen cosmetics. MATERIALS AND METHODS: ZnO nano-particles were incorporated into an ordered mesoporous silica matrix known as Santa Barbara Amorphous-15 (SBA-15), using post-synthesis methodology. The resulting nanocomposites were characterized using X-ray diffraction, small angle X-ray scattering, N2 adsorption-desorption isotherms, Fourier transform infrared spectroscopy, scanning electron microscopy and predicted in vitro sun protector factor (SPF) estimation. Effectiveness and safety were evaluated by antimicrobial activity, in vitro cell toxicity and non-invasive multi-photon tomography with fluorescence lifetime imaging. RESULTS: The structure of the nanocomposites was similar to that of SBA-15, with little perturbation caused by ZnO incorporation. Nanocomposites had an increased in vitro SPF, reduced cytotoxic activity and favourable antimicrobial properties compared to ZnO. ZnO:SBA-15 nanocomposites exhibited no measurable toxicity when applied to human skin in vivo. CONCLUSION: Due to their suitable physicochemical properties and improved safety compared to bare ZnO nanoparticles, the ZnO:SBA-15 nanocomposites show promise for use in cosmetic applications.

Mesoporous Materials: From Synthesis to Applications.

Mesoporous silica are inorganic materials, which are formed by the condensation of sodium silicate or silicon alkoxides around an ordered surfactant used as template [...].

Use of Materials Based on Polymeric Silica as Bone-Targeted Drug Delivery Systems for Metronidazole.

Mesostructured ordered silica-based materials are the promising candidates for local drug delivery systems in bone disease due to their uniform pore size and distribution, and high surface area which affect their excellent adsorption properties, good biocompatibility and bioactivity, and versatile functionalization so that their properties can be controlled. Ordered mesoporous silica (MCM-41 type) was synthesized by a surfactant-assisted sol-gel process using tetraethoxysilane as a silica precursor and hexadecyltrimethylammonium bromide as the structure-directing agent. Functionalized silica materials containing various types of organic groups (3-aminopropyl, 3-mercaptopropyl, or 3-glycidyloxypropyl groups) were synthesized by the post-grafting method onto pre-made mesoporous silica. Comparative studies of their structural characteristics, the surface mineralization activity and release properties for the model drug Metronidazole (MT) were then conducted. It has been found that porosity parameters, mineralization activity and adsorption/release of metronidazole from mesoporous channels of silica can be regulated using functional groups which are chemically bounded with an outer silica surface. The preferential mineral nucleation was found on negatively charged surfaces-MCM-41, and mercaptopropyl and glycidyloxypropyl functionalized silica (MCM-SH and MCM-epoxy, respectively) in simulated body fluid (SBF solution), as well as a sustained release of MT. In contrast to them, aminopropyl-functionalized samples (MCM-NH2) achieved a high MT release rate. These results confirm the potential of silica-based materials for local therapeutic applications (as drug carriers and bone substitutes) in bone disease.