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.

A water-soluble precursor for efficient silica polymerization by silicateins.

Silicateins, the spicule-forming proteins from marine demosponges capable to polymerize silica, are popular objects of biomineralization studies due to their ability to form particles varied in shape and composition under physiological conditions. Despite the occurrence of the many approaches to nanomaterial synthesis using silicateins, biochemical properties of this protein family are poorly characterized. The main reason for this is that tetraethyl orthosilicate (TEOS), the commonly used silica acid precursor, is almost insoluble in water and thus is poorly available for the protein. To solve this problem, we synthesized new water-soluble silica precursor, tetra(glycerol)orthosilicate (TGS), and characterized biochemical properties of the silicatein A1 from marine sponge Latrunculia oparinae. Compared to TEOS, TGS ensured much greater activity of silicatein and was less toxic for the mammalian cell culture. We evaluated optimum conditions for the enzyme - pH range, temperature and TGS concentration. We concluded that TGS is a useful silica acid precursor that can be used for silica particles synthesis and in vivo applications.

pH and Ultrasound Dual-Responsive Polydopamine-Coated Mesoporous Silica Nanoparticles for Controlled Drug Delivery.

A pH- and ultrasound dual-responsive drug release pattern was successfully achieved using mesoporous silica nanoparticles (MSNs) coated with polydopamine (PDA). In this paper, the PDA shell on the MSN surface was obtained through oxidative self-polymerization under the alkaline condition. The morphology and structure of this composite nanoparticle were fully characterized by a series of analyses, such as infrared (IR), transmission electron microscopy, and thermogravimetric analysis. Doxorubicin hydrochloride (DOX)-loaded composite nanoparticles were used to study the performances of responsive drug storage/release behavior, and this kind of hybrid material displayed an apparent pH response in DOX releasing under the acidic condition. Beyond that, upon high-intensity focused ultrasound exposure, loaded DOX in composite nanoparticles was successfully triggered to release from pores because of the ultrasonic cavitation effect, and the DOX-releasing pattern could be optimized into a unique pulsatile fashion by switching the on/off status. From the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, it was observed that our blank nanoparticles showed no toxicity to HeLa cells, but DOX-loaded nanoparticles could inhibit the growth of tumor cells. Furthermore, these composite nanoparticles displayed an effective near-IR photothermal conversion capability with a relatively high conversion efficiency (∼37%). These as-desired drug delivery carriers might have a great potential for future cancer treatment that combine the chemotherapy and photothermal therapy.

Structural, Mechanical, Imaging and in Vitro Evaluation of the Combined Effect of Gd3+ and Dy3+ in the ZrO2-SiO2 Binary System.

Mechanical strength and biocompatibility are considered the main prerequisites for materials in total hip replacement or joint prosthesis. Noninvasive surgical procedures are necessary to monitor the performance of a medical device in vivo after implantation. To this aim, simultaneous Gd3+ and Dy3+ additions to the ZrO2-SiO2 binary system were investigated. The results demonstrate the effective role of Gd3+ and Dy3+ to maintain the structural and mechanical stability of cubic zirconia ( c-ZrO2) up to 1400 °C, through their occupancy of ZrO2 lattice sites. A gradual tetragonal to cubic zirconia ( t-ZrO2 → c-ZrO2) phase transition is also observed that is dependent on the Gd3+ and Dy3+ content in the ZrO2-SiO2. The crystallization of either ZrSiO4 or SiO2 at elevated temperatures is delayed by the enhanced thermal energy consumed by the excess inclusion of Gd3+ and Dy3+ at c-ZrO2 lattice. The addition of Gd3+ and Dy3+ leads to an increase in the density, elastic modulus, hardness, and toughness above that of unmodified ZrO2-SiO2. The multimodal imaging contrast enhancement of the Gd3+ and Dy3+ combinations were revealed through magnetic resonance imaging and computed tomography contrast imaging tests. Biocompatibility of the Gd3+ and Dy3+ dual-doped ZrO2-SiO2 systems was verified through in vitro biological studies.

Synthesis and characterization of manganese containing mesoporous bioactive glass nanoparticles for biomedical applications.

Mesoporous bioactive glass (BG) nanoparticles based in the system: SiO2-P2O5-CaO-MnO were synthesized via a modified Stöber process at various concentrations of Mn (0-7 mol %). The synthesized manganese-doped BG nanoparticles were characterized in terms of morphology, composition, in vitro bioactivity and antibacterial activity. Scanning electron microscopy (SEM), transmission electron microscopy (TEM) and Brunauer-Emmett-Teller (BET) analysis confirmed that the particles had spherical morphology (mean particle size: 110 nm) with disordered mesoporous structure. Energy dispersive X-ray spectroscopy (EDX) confirmed the presence of Mn, Ca, Si and P in the synthesized Mn-doped BG particles. Moreover, X-ray diffraction (XRD) analysis showed that Mn has been incorporated in the amorphous silica network (bioactive glass). Moreover, it was found that manganese-doped BG particles form apatite crystals upon immersion in simulated body fluid (SBF). Inductively coupled plasma atomic emission spectroscopy (ICP-OES) measurements confirmed that Mn is released in a sustained manner, which provided antibacterial effect against Bacillus subtilis, Pseudomonas aeruginosa and Staphylococcus aureus. The results indicate that the incorporation of Mn in the bioactive glass network is an effective strategy to develop novel multifunctional BG nanoparticles for bone tissue engineering.

Silica/Polyethylene Glycol Hybrid Materials Prepared by a Sol-Gel Method and Containing Chlorogenic Acid.

Chlorogenic acid (CGA) is a very common dietary polyphenolic compound. CGA is becoming very attractive due to its potential use as preventive and therapeutic agent in many diseases, including cancer. Inorganic/organic hybrid materials are gaining considerable attention in the biomedical field. The sol-gel process provides a useful way to obtain functional organic/inorganic hybrids. The aim of this study was to synthesize silica/polyethylene glycol (PEG) hybrids with different percentages of CGA by sol-gel technique and to investigate their impact on the cancer cell proliferation. Synthesized materials have been chemically characterized through the FTIR spectroscopy and their bioactivity evaluated looking by SEM at their ability to produce a hydroxyapatite layer on their surface upon incubation with simulated body fluid (SBF). Finally, their effects on cell proliferation were studied in cell lines by direct cell number counting, MTT, flow cytometry-based cell-cycle and cell death assays, and immunoblotting experiments. Notably, we found that SiO2/PEG/CGA hybrids exhibit clear antiproliferative effects in different tumor, including breast cancer and osteosarcoma, cell lines in a CGA dependent manner, but not in normal cells. Overall, our results increase the evidence of CGA as a possible anticancer agent and illustrate the potential for clinical applications of sol-gel synthesized SiO2/PEG/CGA materials.

Asymmetric Silica Nanoparticles with Tunable Head-Tail Structures Enhance Hemocompatibility and Maturation of Immune Cells.

Asymmetric mesoporous silica nanoparticles (MSNs) with controllable head-tail structures have been successfully synthesized. The head particle type is tunable (solid or porous), and the tail has dendritic large pores. The tail length and tail coverage on head particles are adjustable. Compared to spherical silica nanoparticles with a solid structure (Stöber spheres) or large-pore symmetrical MSNs with fully covered tails, asymmetrical head-tail MSNs (HTMSNs) show superior hemocompatibility due to reduced membrane deformation of red blood cells and decreased level of reactive oxygen species. Moreover, compared to Stöber spheres, asymmetrical HTMSNs exhibit a higher level of uptake and in vitro maturation of immune cells including dendritic cells and macrophage. This study has provided a new family of nanocarriers with potential applications in vaccine development and immunotherapy.

A Useful Method for Preparing Mixed Brush Polymer Grafted Nanoparticles by Polymerizing Block Copolymers from Surfaces with Reversed Monomer Addition Sequence.

The preparation of well-defined block copolymers using controlled radical polymerization depends on the proper order of monomer addition. The reversed order of monomer addition results in a mixture of block copolymer and homopolymer and thus has typically been avoided. In this paper, the low blocking efficiency of reversed monomer addition order is utilized in combination with surface initiated reversible addition-fragmentation chain-transfer polymerization to establish a facile procedure toward mixed polymer brush grafted nanoparticles SiO2 -g-(PS (polystyrene), PS-b-PMAA (polymethacrylic acid)). The SiO2 -g-(PS, PS-b-PMAA) nanoparticles are analyzed by gel permeation chromatography deconvolution, and the fraction of each polymer component is calculated. Additionally, the SiO2 -g-(PS, PS-b-PMAA) are amphiphilic in nature and show unique self-assembly behavior in water.

Synthesis of small-sized, porous, and low-toxic magnetite nanoparticles by thin POSS silica coating.

In this communication, we report the synthesis of small-sized (<10 nm), water-soluble, magnetic nanoparticles (MNPs) coated with polyhedral oligomeric silsesquioxanes (POSS), which contain either polyethylene glycol (PEG) or octa(tetramethylammonium) (OctaTMA) as functional groups. The POSS-coated MNPs exhibit superparamagnetic behavior with saturation magnetic moments (51-53 emu g(-1)) comparable to silica-coated MNPs. They also provide good colloidal stability at different pH and salt concentrations, and low cytotoxicity to MCF-7 human breast epithelial cells. The relaxivity data and magnetic resonance (MR) phantom images demonstrate the potential application of these MNPs in bioimaging.

Probing the Role of Zr Addition versus Textural Properties in Enhancement of CO2 Adsorption Performance in Silica/PEI Composite Sorbents.

Polymeric amines such as poly(ethylenimine) (PEI) supported on mesoporous oxides are promising candidate adsorbents for CO2 capture processes. An important aspect to the design and optimization of these materials is a fundamental understanding of how the properties of the oxide support such as pore structure, particle morphology, and surface properties affect the efficiency of the guest polymer in its interactions with CO2. Previously, the efficiency of impregnated PEI to adsorb CO2 was shown to increase upon the addition of Zr as a surface modifier in SBA-15. However, the efficacy of this method to tune the adsorption performance has not been explored in materials of differing textural and morphological nature. Here, these issues are directly addressed via the preparation of an array of SBA-15 support materials with varying textural and morphological properties, as well as varying content of zirconium doped into the material. Zirconium is incorporated into the SBA-15 either during the synthesis of the SBA-15, or postsynthetically via deposition of Zr species onto pure-silica SBA-15. The method of Zr incorporation alters the textural and morphological properties of the parent SBA-15 in different ways. Importantly, the CO2 capacity of SBA-15 impregnated with PEI increases by a maximum of ∼60% with the quantity of doped Zr for a "standard" SBA-15 containing significant microporosity, while no increase in the CO2 capacity is observed upon Zr incorporation for an SBA-15 with reduced microporosity and a larger pore size, pore volume, and particle size. Finally, adsorbents supported on SBA-15 with controlled particle morphology show only modest increases in CO2 capacity upon inclusion of Zr to the silica framework. The data demonstrate that the textural and morphological properties of the support have a more significant impact on the ability of PEI to capture CO2 than the support surface composition.

Multifunctional PEG modified DOX loaded mesoporous silica nanoparticle@CuS nanohybrids as photo-thermal agent and thermal-triggered drug release vehicle for hepatocellular carcinoma treatment.

The combination of a multi-therapeutic mode with a controlled fashion is a key improvement in nanomedicine. Here, we synthesized polyethylene glycol (PEG)-modified doxorubicin (DOX)-loaded mesoporous silica nanoparticle (MSN) @CuS nanohybrids as efficient drug delivery carriers, combined with photothermal therapy and chemotherapy to enhance the therapeutic efficacy on hepatocellular carcinoma (HCC). The physical properties of the nanohybrids were characterized by transmission electron microscopy (TEM), N2 adsorption and desorption experiments and by the Vis-NIR absorption spectra. The results showed that the doxorubicin could be stored in the inner pores of mesoporous silica nanoparticles; the CuS nanoparticles, which are coated on the surface of a mesoporous silica nanoparticle, could serve as efficient photothermal therapy (PTT) agents; the loaded drug release could be easily triggered by NIR irradiation. The combination of the PTT treatment with controlled chemotherapy could further enhance the cancer ablation ability compared to any of the single approaches alone. Hence, the reported PEG-modified DOX-loaded mesoporous silica nanoparticle@CuS nanohybrids might be very promising therapeutic agents for HCC treatment.

An interface-directed coassembly approach to synthesize uniform large-pore mesoporous silica spheres.

A facile and controllable interface-directed coassembly (IDCA) approach is developed for the first time to synthesize uniform discrete mesoporous silica particles with a large pore size (ca. 8 nm) by using 3-dimensional macroporous carbon (3DOMC) as the nanoreactor for the confined coassembly of template molecules and silica source. By controlling the amount of the precursor solution and using Pluronic templates with different compositions, we can synthesize mesoporous silica particles with diverse morphologies (spheres, hollow spheres, and hemispheres) and different mesostructure (e.g., 2-D hexagonal and 3D face centered cubic symmetry), high surface area of about 790 m(2)/g, and large pore volume (0.98 cm(3)/g). The particle size can be tunable from submicrometer to micrometer regimes by changing the macropore diameter of 3DOMC. Importantly, this synthesis concept can be extended to fabricate multifunctional mesoporous composite spheres with a magnetic core and a mesoporous silica shell, large saturated magnetization (23.5 emu/g), and high surface area (280 m(2)/g). With the use of the magnetic mesoporous silica spheres as a magnetically recyclable absorbent, a fast and efficient removal of microcystin from water is achieved, and they can be recycled for 10 times without a significant decrease of removal efficiency for microcystin.

New strategy to prepare hollow silica microspheres with tunable holes on the shell wall.

Hollow silica microspheres with holes of tunable numbers and sizes on the shell wall were prepared in this study. Clusters with positively charged polystyrene (PS) microspheres as the central spheres (CSs) and negatively charged PS spheres as the "halo" spheres (HSs) were formed via electrostatic interactions and utilized as a template. In the subsequent silica coating process, only CS was selectively coated; hence, after calcination, porous hollow silica microspheres were obtained.

Biomimetic sol-gel synthesis of TiO2 and SiO2 nanostructures.

We report the heptapeptide-mediated biomineralization of titanium dioxide nanoparticles from titanium alkoxides. We evaluated the influence of pH on the biomineralized products and found that nanostructured TiO2 was formed in the absence of external ions (water only) at pH ~ 6.5. Several variants (mutants) of the peptides with different properties (i.e., different charges, isoelectric points (pIs), and sequences) were designed and tested in biomineralization experiments. Acid-catalyzed experiments were run using the H1 (HKKPSKS) peptide at room temperature, which produced anatase nanoparticles (~5 nm in size) for the first time via a heptapeptide and sol-gel approach. In addition, the peptide H1 was used to synthesize SiO2 nanoparticles. The influence of the pH and the added ions were monitored: at higher pH levels (8-9), SiO2 nanoparticles (20-30 nm in size) were obtained. In addition, whereas borate and Tris ions allowed the formation of colloidal systems, phosphate ions were unable to produce sols. The results presented here demonstrate that biomineralization depends on the sequence and charge of the peptide, and ions in solution can optimize the formation of nanostructures.

Tuning particle biodegradation through polymer-peptide blend composition.

We report the preparation of polymer-peptide blend replica particles via the mesoporous silica (MS) templated assembly of poly(ethylene glycol)-block-poly(2-diisopropylaminoethyl methacrylate-co-2-(2-(2-(prop-2-ynyloxy)ethoxy)ethoxy)ethyl methacrylate) (PEG45-b-P(DPA55-co-PgTEGMA4)) and poly(l-histidine) (PHis). PEG45-b-P(DPA55-co-PgTEGMA4) was synthesized by atom transfer radical polymerization (ATRP), and was coinfiltrated with PHis into poly(methacrylic acid) (PMA)-coated MS particles assembled from different peptide-to-polymer ratios (1:1, 1:5, 1:10, or 1:15). Subsequent removal of the sacrificial templates and PMA resulted in monodisperse, colloidally stable, noncovalently cross-linked polymer-peptide blend replica particles that were stabilized by a combination of hydrophobic interactions between the PDPA and the PHis, hydrogen bonding between the PEG and PHis backbone, and π-π stacking of the imidazole rings of PHis side chains at physiological pH (pH ∼ 7.4). The synergistic charge-switchable properties of PDPA and PHis, and the enzymatic degradability of PHis, make these particles responsive to pH and enzymes. In vitro studies, in simulated endosomal conditions and inside cells, demonstrated that particle degradation kinetics could be engineered (from 2 to 8 h inside dendritic cells) based on simple adjustment of the peptide-to-polymer ratio used.

The use of in situ and ex situ techniques for the study of the formation mechanism of mesoporous silica formed with non-ionic triblock copolymers.

Since the discovery of the mesoporous silica material templated by ionic surfactants and the subsequent development of materials templated by non-ionic surfactants and polymers, for example SBA-15, there has been a continuous research effort towards understanding their formation. In situ methodologies, such as Small Angle X-ray Scattering (SAXS), Small Angle Neutron Scattering (SANS), spectroscopic techniques like NMR and EPR, and ex situ methodologies such as electron microscopy techniques (SEM, TEM and cryo-TEM) are powerful and important tools in the investigation of the mechanism by which these materials form. The need for a fundamental understanding of the systems is of academic concern and of great importance when developing materials for applications. In this tutorial review we aim to give the reader a comprehensive overview on the development of the field over the years and an introduction to the experimental in situ and ex situ techniques that have been used.

Solid-state NMR studies of micelle-templated mesoporous solids.

In this tutorial review we intend to give an overview of the potential of NMR spectroscopy, and in particular solid-state NMR, in characterising micelle-templated mesoporous materials. Different topics are covered including the study of formation mechanisms, the characterisation of structures, textures, surfaces and interfaces, functionalisation, dynamic properties and structure-reactivity correlations. Some selected examples illustrate the variety of information provided by this spectroscopy. Particular attention is paid to recent technological and/or methodological developments.

Silicateins--a novel paradigm in bioinorganic chemistry: enzymatic synthesis of inorganic polymeric silica.

The inorganic matrix of the siliceous skeletal elements of sponges, that is, spicules, is formed of amorphous biosilica. Until a decade ago, it remained unclear how the hard biosilica monoliths of the spicules are formed in sponges that live in a silica-poor (<50 µM) aquatic environment. The following two discoveries caused a paradigm shift and allowed an elucidation of the processes underlying spicule formation; first the discovery that in the spicules only one major protein, silicatein, exists and second, that this protein displays a bio-catalytical, enzymatic function. These findings caused a paradigm shift, since silicatein is the first enzyme that catalyzes the formation of an inorganic polymer from an inorganic monomeric substrate. In the present review the successive steps, following the synthesis of the silicatein product, biosilica, and resulting in the formation of the hard monolithic spicules is given. The new insight is assumed to open new horizons in the field of biotechnology and also in biomedicine.

Triblock siloxane copolymer surfactant: template for spherical mesoporous silica with a hexagonal pore ordering.

Ordered mesoporous silica materials with a spherical morphology have been prepared for the first time through the cooperative templating mechanism (CTM) by using a silicone triblock copolymer as template. The behavior of the pure siloxane copolymer amphiphile in water was first investigated. A direct micellar phase (L(1)) and a hexagonal (H(1)) liquid crystal were found. The determination of the structural parameters by SAXS measurements leads us to conclude that in the hexagonal liquid crystal phase a part of the ethylene oxide group is not hydrated as observed for the micelles. Mesoporous materials were then synthesized from the cooperative templating mechanism. The recovered materials were characterized by SAXS measurements, nitrogen adsorption-desorption analysis, and transmission and scanning electron microscopy. The results clearly evidence that one can control the morphology and the nanostructuring of the resulting material by modifying the synthesis parameters. Actually, highly ordered mesoporous materials with a spherical morphology have been obtained with a siloxane copolymer/tetramethoxysilane molar ratio of 0.10 after hydrothermal treatment at 100 °C. Our study also supports the fact that the interactions between micelles and the hydrolyzed precursor are one of the key parameters governing the formation of ordered mesostructures through the cooperative templating mechanism. Indeed, we have demonstrated that when the interactions between micelles are important, only wormhole-like structures are recovered.

Preparation of aluminum-containing mesoporous silica with hierarchical macroporous architecture and its enhanced catalytic activities.

Aluminum-containing mesoporous silica with hierarchical macroporous architecture (Al-MMS) was successfully prepared using a solvent evaporation method through the combination of precursor solution for synthesis of Al-containing mesoporous silica (Al-MS) and poly(methyl methacrylate) (PMMA) colloidal crystals as a hard template. The porous structure and the state of aluminum were investigated using various characterization techniques. The construction of combined structure of Al-MMS, i.e., hierarchical macroporous architecture consisting of thin mesoporous silica frameworks, led to the formation of many mesopore entrances and the shortening of the mesoporous channels. In the tetrahydropyranylation of linear alcohols with dihydropyran (DHP), Al-MMS exhibited higher catalytic activities for the formation of corresponding tetrahydropyranyl ethers as compared to Al-MS. The advantageous structure of Al-MMS enables the efficient transport of reactants to the catalytically active sites, which realizes the significant enhancement of catalytic performances in the reaction of DHP with alcohols having longer alkyl chains.