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Understanding lipase-mediated hydrolysis mechanisms within solid-state nanocarriers is fundamental for the rational design of lipid-based formulations. In this study, SBA-15 ordered mesoporous silica (MPS) particles were engineered with well-controlled nanostructural properties to systematically elucidate the role of intrawall microporosity, mesopore size, and particle structure on lipase activity. The microporosity and diffusional path length were shown to be key modulators for lipase-provoked hydrolysis of medium chain triglycerides confined within MPS,with small changes in the pore size, between 9 and 13 nm, showing now a clear correlation to lipase activity. Lipid speciation within MPS after lipolysis, obtained through1H NMR, indicated that free fatty acids preferentially adsorbed to rod-shaped MPS (RodMPS) particles with high microporosity. MPS that formed aggregated spindle-like structures (AggMPS) had intrinsically reduced microporosity, which was hypothesized to limit lipase/lipid diffusion to and from the MPS pores and thus retard lipolysis kinetics. A linear correlation between the microporosity and the extent of lipase-provoked hydrolysis was observed within both AggMPS and RodMPS, ultimately indicating that the intricate interplay between the microporosity and lipid/lipase diffusion can be harnessed to optimize lipolysis kinetics for silica−lipid hybrid carriers. The new insights derived in this study are integral to the future development of solid-state lipid-based nanocarriers that control the lipase activity for improving the absorption of poorly soluble bio-active compounds. Refereed/Peer-reviewed

Gold nanoparticles have the potential to be used in biomedical applications from diagnostics to drug delivery. However, interactions of gold nanoparticles with different biomolecules in the cellular environment result in the formation of a “protein corona”—a layer of protein formed around a nanoparticle, which induces changes in the properties of nanoparticles. In this work we developed methods to reproducibly synthesize spheroidal and star-shaped gold nanoparticles, and carried out a physico-chemical characterization of synthesized anionic gold nanospheroids and gold nanostars through transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential (ZP), nanoparticles tracking analysis (NTA), ultraviolet-visible (UV–Vis) spectroscopy and estimates of surface-enhanced Raman spectroscopy (SERS) signal enhancement ability. We analyzed how they interact with proteins after pre-incubation with bovine serum albumin (BSA) via UV–Vis, DLS, ZP, NTA, SERS, cryogenic TEM (cryo-TEM) and circular dichroism (CD) spectroscopy. The tests demonstrated that the protein adsorption on the particles’ surfaces was different for spheroidal and star shaped particles. In our experiments, star shaped particles limited the protein corona formation at SERS “hot spots”. This benefits the small-molecule sensing of nanostars in biological media. This work adds more understanding about protein corona formation on gold nanoparticles of different shapes in biological media, and therefore guides design of particles for studies in vitro and in vivo.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Here, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model is built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellular-ized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2-3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal com-partments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular Doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diag-nosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model was built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellularized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2–3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development, and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal compartments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diagnosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

Melatonin (MLT) is a pineal hormone involved in the regulation of the sleep/wake cycle. The efficacy of exogenous MLT for the treatment of circadian and sleep disorders is variable due to a strong liver metabolism effect. In this work, MLT is encapsulated in mesoporous silica (AMS-6) with a loading capacity of 28.8 wt%, and the mesopores are blocked using a coating of cellulose acetate phthalate (CAP) at 1:1 and 1:2 AMS-6/MLT:CAP ratios. The release kinetics of MLT from the formulations is studied in simulated gastrointestinal fluids. The permeability of the MLT released from the formulations and its 6-hydroxylation are studied in an in vitro model of the intestinal tract (Caco-2 cells monolayer). The release of MLT from AMS-6/MLT:CAP 1:2 is significantly delayed in acidic environments up to 40 min, while remaining unaffected in neutral environments. The presence of CAP decreases the absorption of melatonin and increases its catabolism into 6-hydroxylation by the cytochrome P450 enzyme CYP1A2. The simple confinement of melatonin into AMS-6 pores slightly affects the permeability and significantly decreases melatonin 6-hydroxylation. Measurable amounts of silicon in the basolateral side of the Caco-2 cell monolayer might suggest the dissolution of AMS-6 during the experiment.

The protein corona of mesoporous silica particles is significantly affected by their morphology, pore structure and size. High aspect ratio particles with large 12 nm pores have a high proportion of low molecular weight proteins in comparison to spherical particles with 5 nm pores, which show a homogenous protein coating which is generally constant in protein composition after long incubation times in serum. The pre-formation of a protein corona prior to incubation with microglia cells enhances the cellular uptake of spherical particles but not facetted or high aspect ratio particles.

Mesoporous silica particles (MSPs) enhance the release kinetics of poorly soluble compound probucol (PB) under the influence of a pore-blocking protein corona, prepared with lysozyme protein adsorption. In vivo oral administration experiments show a prolongation in the time to reach maximum systemic concentration and half-life of PB released from the lysozyme-MSP complex in comparison to the MSP alone. Specific hard protein corona complexes can act as functional diffusion barriers for the controlled release of drugs from MSP based formulations.

The protein corona of nanoparticles is becoming a tool to understand the relation between intrinsic physicochemical properties and extrinsic biological behaviour. A diverse set of characterisation techniques such as transmission electron microscopy, mass spectrometry, dynamic light scattering, zeta-potential measurements and surface enhanced Raman spectroscopy are used to determine the composition and physical properties of the soft and hard corona formed around spherical gold nanoparticles. Advanced characterisation via small angle X-ray scattering and cryo-transmission electron microscopy suggests the presence of a thin hard corona of a few nm on 50 nm gold nanoparticles. The protein corona does not cause changes in cell viability, but inhibits the generation of reactive oxygen species in microglia cells. When a pre-incubated layer of fibrinogen, a protein with high affinity for the gold surface, is present around the nanoparticles before a protein corona is formed in bovine serum, the cellular uptake is significantly increased with an inhibition of ROS. The selective sequential pre-formation of protein complexes prior to incubation in cells is demonstrated as a viable method to alter the biological behaviour of nanoparticles.

Nanodiamonds form a dynamic protein corona independent of the type of surface functional group. Proteomics data suggest that the top 30 proteins of nanodiamonds that are incubated in fetal bovine serum are similar in terms of abundance and function, despite differences in the nanodiamond surface properties. Surprisingly, the most abundant serum protein, albumin, is not one of the most abundant corona proteins, with low molecular weight proteins below 20 kDa being favoured. The pre-incubation of a protein corona on nanodiamonds significantly decreases the production of reactive oxygen species, increasing the cell viability of macrophages after incubation with the nanodiamonds for 48 hours. However, this effect was only observed for protein coronas on nanodiamonds with a negative surface charge and not when they were functionalised with positive surface charges, such as amine groups. This work highlights the role of the protein corona in colloidal stability and its effect on the biological behaviour of diamond nanoparticles.

Mesoporous silica-based particles are promising candidates for biomedical applications. Here, we address the importance of macrophage activation status for internalization of AMS6 (approx. 200 nm in diameter) versus AMS8 (approx. 2 μm) mesoporous silica particles and the role of different phagocytosis receptors for particle uptake. To this end, FITC-conjugated silica particles were used. AMS8 were found to be non-cytotoxic both for M-CSF-stimulated (anti-inflammatory) and GM-CSF-stimulated (pro-inflammatory) macrophages, whereas AMS6 exhibited cytotoxicity towards M-CSF-stimulated, but not GM-CSF-stimulated macrophages; this toxicity was, however, mitigated in the presence of serum. AMS8 triggered the secretion of pro-inflammatory cytokines in M-CSF-activated cells. Class A scavenger receptor (SR-A) expression was noted in both M-CSF and GM-CSF-stimulated macrophages, although the expression was higher in the former case, and gene silencing of SR-A resulted in a decreased uptake of AMS6 in the absence of serum. GM-CSF-stimulated macrophages expressed higher levels of the mannose receptor CD206 compared to M-CSF-stimulated cells, and uptake of AMS6, but not AMS8, was reduced following the downregulation of CD206 in GM-CSF-stimulated cells; particle uptake was also suppressed by mannan, a competitive ligand. These studies demonstrate that macrophage activation status is an important determinant of particle uptake and provide evidence for a role of different macrophage receptors for cell uptake of silica particles.

Han et al. [(2020), IUCrJ, 7, 228–237] using advanced electron microscopy and crystallographic modelling rationalise the microstructure of twinning defects in order to visualize mesophase transitions and surface properties of G and D bicontinuous cubic mesostructured silica. This work furthers our understanding of how these phases originate in many natural and synthetic systems.

Antioxidants play a vital role in scavenging reactive oxygen species (ROS) produced by the reduction of molecular oxygen from various cellular mechanisms. Under oxidative stress, an increase in the levels of ROS overwhelms the antioxidant response, causing oxidative damage to biological molecules, and leading to the development of various diseases. Drug compounds with potent antioxidant properties are typically poorly water soluble and highly hydrophobic. An extreme case is Probucol (PB), a potent antioxidant with reported water solubility of 5 ng/ml, and oral bioavailiability of10%. In this study, PB was loaded in mesoporous silica at various drug loadings to understand the changes to the physical properties of the loaded drug, and it's in vitro drug release. Further in vitro studies were conducted in endothelial and microglia cell models to compare the free radical scavening efficiency of ascorbic acid, PB, and PB release from mesoporous silica particles. Out of the three different mesostructured particles studied, the maximum loading of PB was achieved for large pore mesoporous particles (SBA-15) at 50 wt% drug loading, before complete pore filling was observed. For all materials, loadings above complete pore filling resulted in the recrystallization of PB on the external surface. In vitro drug release measurements showed a rapid dissolution rate at low drug loadings compared to a bimodal release profile of amorphous and crystalline drug at higher drug loadings. PB loaded in mesoporous particle was shown to enhance the antioxidant response to extracellular ROS in the endothelial cell line model, and to intracellular ROS in the microglia cell model. Our results indicate that the antioxidant properties of PB can be significantly improved by using mesoporous silica as a delivery vehicle.

There is conflicting evidence on the clinical efficacy of exogenous melatonin for the treatment of sleep disorders. This may be due to differences in the pharmacokinetic (PK) properties of melatonin formulations used in clinical trials. The aim of this systematic review was to understand the relationship between melatonin formulations and PK parameters and, where possible, the effects on sleep outcomes. To this purpose, we conducted a systematic review and nineteen papers were included. The studies included three melatonin transdermal formulation, thirteen oral formulations, one topical, two buccal, two intravenous and two nasogastric formulations. Seven studies investigated the effect of the melatonin formulation on sleep and six of them found a significant improvement in one or more sleep parameters. The potential for an improved controlled release formulation that delays maximum concentration (Cmax) was identified. The different formulations and doses affect melatonin PK, suggesting that treatment efficacy maybe affected. Based on the current evidence, we are unable to provide recommendations of specific melatonin formulations and PK parameters for specific sleep disorders. Future studies should systematically investigate how different PK parameters of melatonin formulations affect efficacy treatment of sleep as well as circadian disorders.

© 2018 Fluorescent nanodiamonds (NDs) are strong contenders as bio-labels for life science imaging, diagnostics and therapeutics. Ultimately, for their use in biomedical applications, their size should ideally be

A colloidal dispersion of uniform organosilica nanoparticles could be produced via the disassembly of the non-surfactant-templated organosilica powder nanostructured folate material (NFM-1). This unusual reaction pathway was available because the folate and silica-containing moieties in NFM-1 are held together by noncovalent interactions. No precipitation was observed from the colloidal dispersion after a week, though particle growth occurred at a solvent-dependent rate that could be described by the Lifshitz-Slyozov-Wagner equation. An organosilica film that was prepared from the colloidal dispersion adsorbed folate-binding protein from solution but adsorbed ions from a phosphate-buffered saline solution to a larger degree. To our knowledge, this is the first instance of a colloidal dispersion of organosilica nanoparticles being derived from a macroscopic material rather than from molecular precursors.

Pharmaceutical compounds with poor solubility are loaded within mesoporous materials to understand the effect of mesoscale confinement on their dissolution behavior. Structural and calorimetric characterization is combined with atomic pair distribution function analysis probing the interactions between the silica surface and the loaded amorphous compound. While different degrees of amorphism are not identifiable from X-ray diffraction data or calorimetric techniques, the atomic pair distribution function analysis can help identify local ordering of the drug molecules. Together with a list of drug descriptors such as crystallization properties, molecular size, and glass transition temperature, the behavior of encapsulated compounds and their release kinetics may be rationalized. Dissolution experiments confirm that different release rates can be achieved with small differences in mesopore design, such as the presence of micropores in Santa Barbara Amorphous-15 and loading amount.

[EN] The ability of a number of mesoporous silica materials (SBA-15, SBA-3, and MCM-48) to immobilize polyphenol oxidase (PPO) at different pH has been tested. Pore size and volume are the structural characteristics with higher influence on the PPO immobilization. Mesoropous material SBA-15 adsorbs a larger quantity of PPO at pH 4.00 and offers an inhibition of enzymatic activity close the 50% in apple extracts., AEGB acknowledges support from the Swedish Research Council (Grant Number 621-2012-3375), the ARC Centre of Excellence for Nanoscale BioPhotonics (CE140100003), and an ARC Future Fellowship (FT150100342)

There is large interest in replicating biological supramolecular structures in inorganic materials that are capable of mimicking biological properties. The use of 5- guanosine monophosphate in the presence of Na+ and K+ ions as a supramolecular template for the synthesis of well-ordered mesostructured materials is reported here. Mesostructured particles with the confined template exhibit high structural order at both meso- and atomic scales, with a lower structural symmetry in the columnar mesophase. Although a chiral space group can not be deduced from X-ray diffraction, analysis by electron microscopy and circular dichroism confirms a chiral stacking arrangement along the c-axis. Guanosine monophosphate based mesophases thus illustrate the possibility for specific molecular imprinting of mesoporous materials by genetic material and the potential for higher definition in molecular recognition., This work was supported by the Swedish Research Council (A.E.G.B.), and L.A.V. thanks the Spanish Government for financial support (project MAT2012-38429-C04) and D.E.L.I for help with the ICP/MS analysis. We are grateful to Prof. Sven Hovmoller (Stockholm University) for advice and helpful discussions regarding electron crystallography and CRISP. We are indebted to Dr. Isabel Correia (Technical University of Lisbon) for her help with circular dichroism measurements.

Tuberculosis is a major problem in public health. While new effective treatments to combat the disease are currently under development, they tend suffer from poor solubility often resulting in low and/or inconsistent oral bioavailability. Mesoporous materials are here investigated in an in vitro intracellular assay, for the effective delivery of compound PA-824; a poorly soluble bactericidal agent being developed against Tuberculosis (TB). Mesoporous materials enhance the solubility of PA-824; however, this is not translated into a higher antibacterial activity in TB-infected macrophages after 5 days of incubation, where similar values are obtained. The lack of improved activity may be due to insufficient release of the drug from the mesopores in the context of the cellular environment. However, these results show promising data for the use of mesoporous particles in the context of oral delivery with expected improvements in bioavailability.

Aim: To study the adjuvant effect of mesoporous silica particles and their capability of modifying an already existing allergic Th2-like immune response. Materials & methods: The adjuvant effect of Santa Barbara Amorphous-15 (SBA-15) mesoporous silica particles was studied in an antigen-specific ovalbumin (OVA) system in vitro and in vivo. The capacity of the OVA-loaded SBA-15 particles (SBA-15-OVA) to modify an existing immune response was assessed in a murine allergy model. Results: SBA-15-OVA induced significantly stronger OVA-specific splenocyte proliferation compared with OVA alone. Significantly higher IFN-γ production was observed in ex vivo OVA-stimulated splenocytes from SBA-15-OVA-immunized mice compared with mice injected with only SBA-15 or OVA. Treatment of OVA-sensitized mice with SBA-15-OVA modified the immune response with significantly lower serum levels of OVA-specific IgE and higher IgG levels compared with the alum-OVA-treated group. Conclusion: The results are promising for the continued development of mesoporous silica materials for therapeutic applications. Original submitted 18 January 2013; Revised submitted 30 August 2013

Ordered nanoporous structures are among the most fascinating and industrially important materials currently in use. The archetypal zeolite material has now been joined by an eclectic array of new structures that exhibit porosity over a wide range of length scales and with order/disorder expressed in a multitude of ways. This raises the bar in terms of characterization and extends a real challenge to the scientific community to fully understand the properties and potential future applications of such materials. In this review we discuss the importance of modern microscopy tools combined with diffraction in this endeavour and show how the details of even the most complex quasi-crystalline nanoporous architectures can be elucidated. We show by using the appropriate spherical aberration (C-s) corrections in scanning transmission electron microscopy it is possible to decipher all the individual silicon and aluminum atoms in a zeolite structure. Automated routines for using large electron diffraction datasets for crystal structure determination of nanocrystals is described making the need for large single crystal synthesis less-and-less important. The power of complementary combinations of surface tools such as atomic force microscopy and high-resolution scanning electron microscopy is discussed to elucidate crystal growth mechanisms. For mesoporous materials synthesized from self-organized organic mesophases electron microscopy reveals the details of the complex hierarchy of porosity so crucial for the functional performance of the structure.

Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation.

Background: Mesoporous silica particles are highly promising nanomaterials for biomedical applications. They can be used to improve bioavailability, solubility and drug stability and to protect drugs from the acidic conditions of the stomach, leading to increased drug effectiveness. Their biocompatibility in vivo has recieved little attention, in particular regarding oral administration. Aim: To study the oral tolerance of micron-sized nanoporous folic acid-templated material-1 (cylindrical, 2D hexagonal pore structure) and nanometer-sized anionic-surfactant-templated mesoporous silica material-6 (cylindrical, 3D cubic pore structure) mesoporous silica particles in Sprague Dawley rats. Materials & methods: A dose stepwise procedure or range finding test was followed by a consequent confirmatory test. The confirmatory test included daily administrations of 2000 and 1200 mg/kg doses for nanoporous folic acid-templated material-1 and anionic-surfactant-templated mesoporous silica material-6, respectively. Results: The maximum tolerated dose for anionic-surfactant-templated mesoporous silica material-6 was not reached. Similar results were observed for nanometer-sized anionic-surfactant-templated mesoporous silica material-1 in most of the animals, although adverse effects were observed in some animals that are most probably due to the administration by oral gavage of the formulated particles. Conclusion: The results are promising for the use of mesoporous silica materials as drug-delivery systems in oral administration. Original submitted 8 February 2012; Revised submitted 30 April 2012; Published online 14 August 2012

Microsomal glutathione transferase 1 (MGST1) is an antioxidant enzyme located predominantly in the mitochondrial outer membrane and endoplasmic reticulum and has been shown to protect cells from lipid peroxidation induced by a variety of cytostatic drugs and pro-oxidant stimuli. We hypothesized that MGST1 may also protect against nanomaterial-induced cytotoxicity through a specific effect on lipid peroxidation. We evaluated the induction of cytotoxicity and oxidative stress by TiO(2), CeO(2), SiO(2), and ZnO in the human MCF-7 cell line with or without overexpression of MGST1. SiO(2) and ZnO nanoparticles caused dose- and time-dependent toxicity, whereas no obvious cytotoxic effects were induced by nanoparticles of TiO(2) and CeO(2). We also noted pronounced cytotoxicity for three out of four additional SiO(2) nanoparticles tested. Overexpression of MGST1 reversed the cytotoxicity of the main SiO(2) nanoparticles tested and for one of the supplementary SiO(2) nanoparticles but did not protect cells against ZnO-induced cytotoxic effects. The data point toward a role of lipid peroxidation in SiO(2) nanoparticle-induced cell death. For ZnO nanoparticles, rapid dissolution was observed, and the subsequent interaction of Zn(2+) with cellular targets is likely to contribute to the cytotoxic effects. A direct inhibition of MGST1 by Zn(2+) could provide a possible explanation for the lack of protection against ZnO nanoparticles in this model. Our data also showed that SiO(2) nanoparticle-induced cytotoxicity is mitigated in the presence of serum, potentially through masking of reactive surface groups by serum proteins, whereas ZnO nanoparticles were cytotoxic both in the presence and in the absence of serum.

We studied equilibrium adsorption and uptake kinetics and identified molecular species that formed during sorption of carbon dioxide on amine-modified silica. Bicontinuous silicas (AMS-6 and MCM-48) were postsynthetically modified with (3-aminopropyl)triethoxysilane or (3-aminopropyl)methyldiethoxysilane, and amine-modified AMS-6 adsorbed more CO(2) than did amine-modified MCM-48. By in situ FTIR spectroscopy, we showed that the amine groups reacted with CO(2) and formed ammonium carbamate ion pairs as well as carbamic acids under both dry and moist conditions. The carbamic acid was stabilized by hydrogen bonds, and ammonium carbamate ion pairs formed preferably on sorbents with high densities of amine groups. Under dry conditions, silylpropylcarbamate formed, slowly, by condensing carbamic acid and silanol groups. The ratio of ammonium carbamate ion pairs to silylpropylcarbamate was higher for samples with high amine contents than samples with low amine contents. Bicarbonates or carbonates did not form under dry or moist conditions. The uptake of CO(2) was enhanced in the presence of water, which was rationalized by the observed release of additional amine groups under these conditions and related formation of ammonium carbamate ion pairs. Distinct evidence for a fourth and irreversibly formed moiety was observed under sorption of CO(2) under dry conditions. Significant amounts of physisorbed, linear CO(2) were detected at relatively high partial pressures of CO(2), such that they could adsorb only after the reactive amine groups were consumed. authorCount :7

Helical organosilica materials were synthesized for the first time using a novel binaphthyl-based chiral co-monomer in less than 1 hour. The incorporation of a chiral co-monomer in the wall was shown to influence the curvature of the helical materials. As the amount of the chiral co-monomer was increased, the degree of curvature increased, illustrating the importance of this monomer to the overall morphology.

The pressure-swing adsorption method for carbon dioxide capture would ideally be facilitated by adsorbents with a high capacity and a high selectivity for CO(2). Several aluminophosphates with 8-ri ...

The fine structural details of mesoporous materials possessing Pmn symmetry prepared with varying amphiphilic surfactants under acid and alkaline conditions are investigated using electron crystall ...

Adsorption-mediated CO(2) separation can reduce the cost of carbon capture and storage. The reduction in cost requires adsorbents with high capacities for CO(2) sorption and high CO(2)-over-N(2) selectivity. Amine-modified sorbents are promising candidates for carbon capture. To investigate the details of CO(2) adsorption in such materials, we studied mesocaged (cubic, Pm3n symmetry) silica adsorbents with tethered propylamines using Fourier transform infrared (FTIR) spectroscopy and volumetric uptake experiments. The degree of heterogeneity in these coatings was varied by either cosynthesizing or postsynthetically introducing the propylamine modification. In situ FTIR spectroscopy revealed the presence of both physisorbed and chemisorbed CO(2) in the materials. We present direct molecular evidence for physisorption using FTIR spectroscopy in mesoporous silica sorbents modified with propylamines. Physisorption reduced the CO(2)-over-N(2) selectivity in amine-rich sorbents. Samples with homogeneous coatings showed typical CO(2) adsorption trends and large quantities of IR-observable physisorbed CO(2). The uptake of CO(2) in mesocaged materials with heterogeneous propylamine coatings was higher at high temperatures than at low temperatures. At higher temperatures and low pressures, the postsynthetically modified materials adsorbed more CO(2) than did the extracted ones, even though the surface area after modification was clearly reduced and the coverage of primary amine groups was lower. The principal mode of CO(2) uptake in postsynthetically modified mesoporous silica was chemisorption. The chemisorbed moieties were present mainly as carbamate-ammonium ion pairs, resulting from the quantitative transformation of primary amine groups during CO(2) adsorption as established by NIR spectroscopy. The heterogeneity in the coatings promoted the formation of these ion pairs. The average propylamine-propylamine distance must be small to allow the formation of carbamate-propylammonium ion pairs.

The development of nanoparticles for biomedical applications including medical imaging and drug delivery is currently undergoing a dramatic expansion. However, as the range of nanoparticle types and applications increases, it is also clear that the potential toxicities of these novel materials and the properties driving such toxic responses must also be understood. Indeed, a detailed assessment of the factors that influence the biocompatibility and/or toxicity of nanoparticles is crucial for the safe and sustainable development of the emerging nanotechnologies. This review summarizes some of the recent developments in the field of nanomedicine with particular emphasis on inorganic nanoparticles for drug delivery. The synthesis routes, physico-chemical characteristics, and cytotoxic properties of inorganic nanoparticles are thus explored and lessons learned from the toxicological investigation of three common types of engineered nanomaterials of titania, gold, and mesoporous silica are discussed. Emphasis is placed on the recognition versus non-recognition of engineered nanomaterials by the immune system, the primary surveillance system against microorganisms and particles, which, in turn, is intimately linked to the issue of targeted drug delivery using such nanomaterials as carrier systems.

A new method to investigate the effect of pore geometry on diffusion processes in mesoporous silica nanoparticles and other types of micro- and mesoporous structures is put forward. The method is based on the study of proton diffusion from a liquid surrounding the mesoporous particles into the particle pore system. The proton diffusion properties are assessed for a variety of as-synthesized mesoporous nano- and microparticles with two-dimensional and three-dimensional connectivity. Results show that the diffusion coefficients are higher for the proton absorption process than for the release of surfactant template molecules, and that they overall follow the same trend with the more complex three-dimensional mesocaged particles showing the highest diffusion coefficients. The pore geometry (cylindrical pores versus cage-type pores) and structure connectivity are found to play a key role for the effects observed. The results put forward in the present work should offer a valuable tool in the development of porous nanomaterials in a range of applications including the use as catalysis and separation enhancers in the petrochemical industry, as scaffolds for hydrogen storage, and as drug delivery vehicles for sustained release and gene transfection.

The synthesis of cubic Pm3n mesocaged solid templated by cetyltrimethyl ammonium bromide (C16TMABr) surfactant by direct cocondensation of (3-aminopropyl)triethoxysilanes (APES) under strong alkaline conditions is reported. The novel route gives direct incorporation of amino functional groups on the porous silica wall, and the structural formation has been followed by means of in situ SAXS studies performed at a synchrotron beam line. Data shows that a molar ratio of C16TMABr/APES = 0.6 favors the formation of 3D cubic mesocaged solid with Pm3n symmetry which transforms to a cylindrical mesoporous phase with p6mm symmetry at higher molar ratios. Further structural evaluation has been performed by means electron crystallography (EC). Reconstructed 3D models based on EC show the presence of spherical cages (A-cages, 45 angstroms) and ellipsoidal cages (B-cages, 48 x 43 angstroms) whereby every cage in the unit cell is connected to 14 nearest cages with a window size of 18 angstroms. Finally, a mechanism is proposed, denoted S+ approximately NoI-, in which penetration of the neutral aminopropyl moiety within the micellar corona is responsible for the formation of the Pm3n phase, accounting for the formation of the hexagonal phase at higher molar ratios and higher temperatures. In comparison to other mesocaged materials with the same symmetry this structure possesses a more open porous network which will help assess its potential in a variety of applications discussed herein.

We present here a detailed study of the controlled release of amino acid derived amphiphilic molecules from the internal pore structure of mesoporous nanoparticle drug delivery systems with different structural properties; namely cubic and hexagonal structures of various degrees of complexity. The internal pore surface of the nanomaterials presented has been functionalised with amine moieties through a one pot method. Release profiles obtained by Alternating Ionic Current measurements are interpreted in terms of specific structural and textural parameters of the porous nanoparticles such as pore geometry and connectivity. Results indicate that diffusion coefficients are lower by as much as four orders of magnitude in 2-dimensional structures in comparison to 3-dimensional mesoporous solids. A fast release in turn is observed from mesocaged materials AMS-9 and AMS-8 where the presence of structural defects is thought to lead to a slightly lower diffusion coefficient in the latter. Amount of pore wall functionalisation and number of binding sites on the model drug are found to have little effect on the drug release rate.

The controlled synthesis of ordered anionic surfactant templated mesoporous silica with cubic Ia3 structure (AMS-6) is reported via prolonged periods of hydrothermal treatment (HT). The cubic Ia3 m ...

The effects of mesoporous silica nano- (270 nm) and microparticles (2.5 microm) with surface areas above 500 m2/g were evaluated on human monocyte-derived dendritic cells (MDDC). Size- and concentration-dependent effects were seen where the smaller particles and lower concentrations affected MDDC to a minor degree compared to the larger particles and higher concentrations, both in terms of viability, uptake, and immune regulatory markers. Our findings support the further development of mesoporous silica particles in drug and vaccine delivery systems.

The purpose of this work is to study the kinetics of self-assembly in the formation mechanism of anionic templated mesoporous solids (AMS-n) during the first few seconds of the synthesis as well as to demonstrate the use of alternating ion current (AIC) conductivity measurements to follow the self-assembly in complex hybrid systems. The formation of different AMS-n caged-type mesostructures through the delayed addition of the silica source is demonstrated and explained in terms of the interaction between the co-structure-directing agent (CSDA) and the oppositely charged surfactant headgroup regions. Our findings, supported by transmission electron microscopy, 29Si magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, dynamic light scattering (DLS) measurements, and powder X-ray diffraction suggest that the interaction of the CSDA with the surfactant headgroup occurs within seconds after its addition to the synthesis gel leading to interaction between the polymerizing CSDAs and the oppositely charged micelle and to an increase in the micelle-CSDA aggregate size. Both DLS and AIC measurements agree that this process occurs within the first 1000 s after addition of the CSDA to the synthesis gel at room temperature. In addition to the mechanistic study it was found that the intermediate materials are comprised of a three-layer entity. Time-dependent 29Si MAS NMR studies reveal that an organo-silica layer forms around the micelles prior to a condensed outer inorganic shell of silica.

While our understanding of the molecular events leading to disease onset and progression have increased exponentially, our capacity to therapeutically intervene in these events with new chemical diversity has clearly fallen short of that pace. In the quest to readdress this situation, the drug discovery sector is slowly but increasingly exploring sources of alternative chemical matter, such as the ones provided by material science and nanotechnology. While new functional nano-sized materials hold great promise for the future, our lack of understanding of the long term safety implications associated with systemic exposure as well as the unclear regulatory path ahead hamper their present impact in drug development. Paradoxically, the exploitation of novel, functionally active micron-sized, synthetic, non-absorbable chemical matter, for the treatment or prevention of a number of epidemiologically significant conditions remains clearly underexplored. A combination of pre-existing evidence and future potential indicates that micron-sized mesoporous silica materials could be an untapped source of new drug candidates. These are free from both the dreaded high attrition associated with small molecule drug discovery and the uncertainties of nano-size technologies. This, together with the coming of age of synthetic methodologies to control particle size and shape; pore size and geometry; surface chemistry, bioconjugation and formulation, open up exciting possibilities to exploit this novel chemistry-biology therapeutic interface.

The effect of the co-condensation of 3-mercaptopropyltriethoxysilane (MPTES) in the preparation of mesoporous silicas has been examined for levels of MPTES of 0–10 mol% (based on silicon) in reported syntheses using the block co-polymers P123 and F127. In syntheses using P123, SBA-15 (p6mm) forms with 0–5 mol% MPTES whereas addition of 7 mol% of the silane results in highly ordered Ia 3 ¯ d silica. Using F127, synthesis in the absence of MPTES gives the reported cubic Fm3m FDU-12 structure, based on the cubic close packing of surfactant micelles, whereas addition of MPTES results in the introduction of a high concentration of stacking defects in the close packing sequences and changes in particle morphology. At 5 mol% MPTES, tapered hexagonal prismatic particles with nano-domains of the hexagonally close packed structure (space group P63/mmc) are obtained. The accessible thiol contents in the members of these two series of solids have been determined using Ellman’s reagent (5,5′-dithiobis-(2-nitrobenzoic acid)): values of 50–70% of the thiols incorporated in the solid have been measured as being accessible to this reactant.

A novel mesoporous material prepared using the recently reported co-assembly of anionic surfactants with organosilane groups has been studied in depth using high-resolution transmission electron microscopy (HRTEM) and electron crystallography. A three-dimensional (3D) structural solution of AMS-8 was obtained by Fourier analysis of HRTEM images, revealing a complex cubic mesocaged solid (space group Fd3m) composed of bimodal cages 3D-connected by cage windows. HRTEM images also indicate the presence of structural defects associated with the cubic close packing of spheres, while analysis by nitrogen adsorption−desorption isotherms reveals that accessibility to smaller cages may be restricted in this material. The opened and closed models of this structure derived from a combination of electron crystallography and nitrogen adsorption data are discussed with respect to the arrangement of cages and cage connectivities. Considerations of the nature of the micellar system playing part in this novel templating ...

Aim: Stem cell-derived motor neurons (MNs) are utilized to develop replacement strategies for spinal cord disorders. Differentiation of embryonic stem cells into MN precursors involves factors and their repeated administration. We investigated if delivery of factors loaded into mesoporous nanoparticles could be effective for stem cell differentiation in vitro. Materials & methods: We used a mouse embryonic stem cell line expressing green fluorescent protein under the promoter for the MN-specific gene Hb9 to visualize the level of MN differentiation. The differentiation of stem cells was evaluated by expression of MN-specific transcription factors monitored by quantitative real-time PCR reactions and immunocytochemistry. Results: Mesoporous nanoparticles have strong affiliation to the embryoid bodies, penetrate inside the embryoid bodies and come in contact with differentiating cells. Conclusion: Repeated administration of soluble factors into a culture medium can be avoided due to a sustained release effect using mesoporous silica. Original submitted 28 August 2013; Revised submitted 23 January 2014

The mesoporous solid SBA-2, prepared at room temperature in alkaline pH using the gemini surfactant [CH3(CH2)15N(CH3)2(CH2)3N(CH3)3]2+ can adopt hollow sphere (ca. 100 μm diameter), flat plate (50 μm across) and small sphere (1–2 μm diameter) morphologies. Plates appear to be formed directly by fracturing of the hollow spheres. The nanostructure of these materials is consistent with templating around close packed micelles. X-Ray diffraction and high resolution imaging show that the structure of these preparations ranges from mainly hexagonal to mainly cubic close packing.