Uptake and cellular distribution, in four plant species, of fluorescently labeled mesoporous silica nanoparticles

Monodispersed mesoporous silica nanoparticles (MSNs) of optimal size and configuration were synthesized for uptake by plant organs, tissues and cells. These monodispersed nanoparticles have a size of 20 nm with interconnected pores with an approximate diameter of 2.58 nm.

Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery.

Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. However, the non-ionic surfactant templated HMSNs often have a broad size distribution and a defective mesoporous structure because of the difficulties involved in controlling the formation and organization of micelles for the growth of silica framework. In this paper, a novel "Eudragit assisted" strategy has been developed to fabricate HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self-assembly of micelle organisation. Highly dispersed mesoporous silica spheres with intact hollow interiors and through pores on the shell were fabricated. The HMSNs have a high surface area (670m(2)/g), small diameter (120nm) and uniform pore size (2.5nm) that facilitated the effective encapsulation of 5-fluorouracil within HMSNs, achieving a high loading capacity of 194.5mg(5-FU)/g(HMSNs). The HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell internalization. The high specificity and excellent targeting performance of EGF grafted HMSNs have demonstrated that they can become potential intracellular drug delivery vehicles for colorectal cancers via EGF-EGFR interaction.

Functionalization of hollow mesoporous silica nanoparticles for improved 5-fu loading

 Hollow mesoporous silica nanoparticles were successfully fabricated and functionalized with appropriate silanes. After modifications, amine, carboxyl, cyano, and methyl groups were grafted onto the nanoparticles and all functionalized hollow mesoporous silica nanoparticles maintained a spherical and hollow structure with a mean diameter of ~120 nm and a shell thickness of ~10 nm. The loading capacity of the hollow mesoporous silica nanoaprticles to the anticancer drug, 5-fluorouracil, can be controlled via precise functionalization. The presence of amine groups on the surface of nanoparticles resulted in the highest loading capacity of 28.89%, due to the amine functionalized nanoparticles having a similar hydrophilicity but reverse charge to the drug. In addition, the change in pH leads to the variation of the intensity of electrostatic force between nanoparticles and the drug, which finally affects the loading capacity of amine functionalized hollow mesoporous silica nanoparticles to some extent. Higher drug loading was observed at pH of 7.4 and 8.5 as 5-fluorouracil becomes more deprotonated in alkaline conditions. The improved drug loading capacity by amine functionalized hollow mesoporous silica nanoparticles has demonstrated that they can become potential intracellular 5-fluorouracil delivery vehicles for cancers.

Tailored hollow mesoporous silica nanoplatforms with biological labels for colon targeted drug deliver systems

Hollow mesoporous silica nanoparticles (HMSNs) were synthesized via a new strategy. HMSNs have a high drug loading, controlled release behaviour, and specifically targeting when bioconjugated with Epidermal Growth Factor. The promising in vitro cell tests have revealed the great potential of the HMSNs to be used for cancer therapy.

Functionalized mesoporous silica nanoparticles with redox-responsive short-chain gatekeepers for agrochemical delivery.

The controlled release of salicylic acid (SA), a key phytohormone, was mediated by using a novel decanethiol gatekeeper system grafted onto mesoporous silica nanoparticles (MSNs). The decanethiol was conjugated only to the external surfaces of the MSNs through glutathione (GSH)-cleavable disulfide linkages and the introduction of a process to assemble gatekeepers only on the outer surface so that the mesopore area can be maintained for high cargo loading. Raman and nitrogen sorption isotherm analyses confirmed the successful linkage of decanethiol to the surface of MSNs. The in vitro release of SA from decanethiol gated MSNs indicated that the release rate of SA in an environment with a certain amount of GSH was significantly higher than that without GSH. More importantly, in planta experiments showed the release of SA from decanethiol gated MSNs by GSH induced sustained expression of the plant defense gene PR-1 up to 7 days after introduction, while free SA caused an early peak in PR-1 expression which steadily decreased after 3 days. This study demonstrates the redox-responsive release of a phytohormone in vitro and also indicates the potential use of MSNs in planta as a controlled agrochemical delivery system.

Functionalized mesoporous silica nanoparticles for smart agrochemical delivery system

The agrochemical delivery system has been built up based on mesoporous silica nanoparticles as carriers in a controllable fashion. Several peer reviewed papers have been published with this research work. This delivery system will benefit for the future agricultural application.

Overcoming acquired drug resistance in colorectal cancer cells by targeted delivery of 5-FU with EGF grafted hollow mesoporous silica nanoparticles

Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest.

A new insight into growth mechanism and kinetics of mesoporous silica nanoparticles by in situ small angle x-ray scattering

The growth mechanism and kinetics of mesoporous silica nanoparticles (MSNs) were investigated for the first time by using a synchrotron time-resolved small-angle X-ray scattering (SAXS) analysis. The synchrotron SAXS offers unsurpassed time resolution and the ability to detect structural changes of nanometer sized objects, which are beneficial for the understanding of the growth mechanism of small MSNs (∼20 nm). The Porod invariant was used to quantify the conversion of tetraethyl orthosilicate (TEOS) in silica during MSN formation, and the growth kinetics were investigated at different solution pH and temperature through calculating the scattering invariant as a function of reaction time. The growth of MSNs was found to be accelerated at high temperature and high pH, resulting in a higher rate of silica formation. Modeling SAXS data of micelles, where a well-defined electrostatic interaction is assumed, determines the size and shape of hexadecyltrimethylammonium bromide (CTAB) micelles before and after the addition of TEOS. The results suggested that the micelle size increases and the micelle shape changes from ellipsoid to spherical, which might be attributed to the solubilization of TEOS in the hydrophobic core of CTAB micelles. A new "swelling-shrinking" mechanism is proposed. The mechanism provides new insights into understanding MSN growth for the formation of functional mesoporous materials exhibiting controlled morphologies. The SAXS analyses were correlated to the structure of CTAB micelles and chemical reaction of TEOS. This study has provided critical information to an understanding of the growth kinetics and mechanism of MSNs.

The control of epidermal growth factor grafted on mesoporous silica nanoparticles for targeted delivery

The performance of biomaterials in a biological environment is largely influenced by the surface properties of the biomaterials. In particular, grafted targeting ligands significantly impact the subsequent cellular interactions. The utilisation of a grafted epidermal growth factor (EGF) is effective for targeted delivery of drugs to tumours, but the amount of these biological attachments cannot be easily quantified as most characterization methods could not detect the extremely low amount of EGF ligands grafted on the surface of nanoparticles. In this study, hollow mesoporous silica nanoparticles (HMSNs) were functionalized with amine groups to conjugate with EGFs via carbodiimide chemistry. Time of flight secondary ion mass spectrometry (ToF-SIMS), a very surface specific technique (penetration depth <1.5 nm), was employed to study the binding efficiency of the EGF to the nanoparticles. Principal component analysis (PCA) was implemented to track the relative surface concentrations of EGFs on HMSNs. It was found that ToF-SIMS combined with the PCA technique is an effective method to evaluate the immobilization efficiency of EGFs. Based on this useful technique, the quantity and density of the EGF attachments that grafted on nanoparticles can be effectively controlled by varying the EGF concentration at grafting stages. Cell experiments demonstrated that the targeting performance of EGFR positive cells was affected by the number of EGFs attached on HMSNs.

A facile synthesis of mesoporous silica nanoparticle and its morphology manipulation by varying pH value

 Mesoporous silica nanoparticles (MSNs) with particle size of20 nm have been synthesised through the template directed method at low temperature. The pH value of the reaction solution was found to have a great impact on the morphology of the final products. The morphology of resultant MSNs were investigated through transmission electron microscope. The mesoporous structure was examined by Brunauer-Emmett-Teller and Barrett-Joyner-Halenda methods. The results suggested that the high pH value had a great effect on the morphology of the final MSNs. Higher pH value intensified the interaction between particles. The pH value less than 10 is good for the formation of nanoparticles, while at pH 12, a silica framework with heterogeneous mesopore structure can be obtained.

Mesoporous silica nanoparticles enhance seedling growth and photosynthesis in wheat and lupin

The application of mesoporous silica nanoparticles (MSNs) as a smart delivery system to agricultural crops is gaining attention but the release of nanoparticles into the environment may pose a potential threat to biological systems. We investigated the effects of MSNs on the growth and development of wheat and lupin plants grown under controlled conditions. We report a dramatic increase in the growth of wheat and lupin plants exposed to MSNs. We also found that, in leaves, MSNs localised to chloroplasts and that photosynthetic activity was significantly increased. In addition, absorption and cellular distribution of MSNs by the two plant species following root uptake were observed using scanning electron microscopy equipped with energy dispersive spectroscopy (SEM-EDS). Following uptake of MSNs at 500 and 1000 mg L(-1), there was enhancement of seed germination, increased plant biomass, total protein and chlorophyll content. Treatment of both species with MSNs at the highest concentration (2000 mg L(-1)) did not result in oxidative stress or cell membrane damage. These findings show that MSNs can be used as novel delivery systems in plants and that over the range of concentrations tested, MSNs do not have any negative impacts on plant growth or development.

Rhodamine 6G encapsuled mesoporous silica channels

We report the effect of solvent on the rhodamine 6G encapsuled into channels of mesoporous silica, synthesized by two-step process that gives intermediary stable hybrid micelles. Mesoporous materials have been obtained by the method that involves surfactant micelles (mainly cationic) and inorganic precursor of the structure to be obtained. MSU-X type mesoporous silica has been synthesized with polyethylene oxide surfactant as the directing-structure agent and tetraethyl orthosilicate Si(OEt)(4) as the silica source. The influence of the solvent on the encapsulation of rhodamine dye was systematically explored, specially its influence on the luminescence properties. Rhodamine 6G encapsuled into mesoporous silica channel was characterized by UV-Vis and luminescence spectroscopies, scanning electron microscopy, small angle x ray scattering and N(2) sorption-desorption. The pore size and the solvent effects into luminescence dye encapsuled into mesoporous silica channels are observed in the visible absorption and emission spectra of rhodamine 6G. The intense photo luminescence band of rhodamine 6G dye is in 500 to 600 nm region. The observed shift of the absorption and emission bands can be assigned to the effect of the solvents dielectric constant and pore size of mesoporous silica.

On the specific filtration mechanism of a mesoporous silica membrane, prepared with non-connecting parallel pores

We report the singular filtration properties of an ultrafiltration membrane made with mesoporous silica that exhibits cylindrical pores aligned mostly normal to the support. This membrane supported on tubular commercial macroporous alumina supports was prepared by the interfacial growth mechanism between stable silica-surfactant hybrid micelles made of the association of silica oligomers with polyethyleneoxide-based (PEO) surfactants and sodium fluoride, a well-known silica condensation catalyst [Boissière et al., An ultrafiltration membrane made with mesoporous MSU-X silica, Chem. Mater. 15 (2003) 460-463]. It appears that the combined effect of the silica nature of the membrane, whose surface charge can be easily adjusted by changing the pH and the non-connected cylindrical shape of the pores provides a new behavior in the retention properties, as proved by the filtration of polyoxyethylene polymers (PEO) with different molecular weights. Depending on the filtration conditions, a rejection rate of 80% and a steep cut-off at 2000 Da can be obtained or, on the reverse, polymers three times bigger than the pore diameter can diffuse through the membrane. This new filtration mechanism, which opens up new modes of separation modes, is explained in the light of both topology of the porous network and pH-dependent interactions between PEO polymers and silica porous media. © 2004 Elsevier B.V. All rights reserved.

An ultrafiltration membrane, prepared with MSU-type mesoporous silica: Preparation and specific filtration behavior

We report preparation and the singular filtration properties of an ultrafiltration membrane made with MSU-type mesoporous silica that exhibits cylindrical pores aligned mostly normal to the support. This membrane supported on tubular commercial macroporous alumina supports was prepared by the interfacial growth mechanism between stable silica-surfactant hybrid micelles made of the association of silica oligomers with polyethyleneoxide-based (PEO) surfactants and sodium fluoride, a well-known silica condensation catalyst. It appears that the combined effect of the silica nature of the membrane, whose surface charge can be easily adjusted by changing the pH and the non-connected cylindrical shape of the pores provides a new behavior in the retention properties, as proved by the filtration of polyoxyethylene polymers (PEO) with different molecular weights. Depending on the filtration conditions, a rejection rate of 80 % and a steep cut-off at 2,000 Da can be obtained or, on the reverse, polymers three times bigger than the pore diameter can diffuse through the membrane. This new filtration mechanism, which opens up new modes of separation modes, is explained in the light of both topology of the porous network and pH-dependent interactions between PEO polymers and silica porous media. © 2005 Elsevier B.V. All rights reserved.