Molecular Elucidation of Biological Response to Mesoporous Silica Nanoparticles in Vitro and in Vivo.

Biomedical applications of mesoporous silica nanoparticles (MSNs) require efficient cellular uptake and low toxicity. The purpose of this study is to investigate the cellular uptake and toxicity of MSNs with different sizes and charges (50, 100, and 250 nm with a positive surface charge and 100 nm with a negative surface charge) exposed to human monocyte-derived macrophages, lung epithelium BEAS-2B cells, and mice using genome-wide gene expression analysis and cellular/animal-level end point tests. We found that MSNs can be taken up into cells through endocytosis in a charge- and size-dependent manner, with positively charged and larger MSNs being more easily taken up into the cells by recruiting more types of endocytotic pathways for more cellular uptake.

Local pH tracking in living cells.

Continuous and simultaneous 3D single-particle movement and local pH detection in HeLa cells were demonstrated for the first time by combining fluorescent mesoporous silica nanoparticles (FMSNs) and a single-particle tracking (SPT) technique with a precision of ∼10 nm. FMSNs, synthesized by the co-condensation of both pH-sensitive and reference dyes with a silica/surfactant source, allow long-term reliable ratiometric pH measurements with a precision better than 0.3 pH unit because of their excellent brightness and stability.

Enzyme encapsulated hollow silica nanospheres for intracellular biocatalysis.

Hollow silica nanospheres (HSN) with low densities, large interior spaces and permeable silica shells are suitable for loading enzymes in the cavity to carry out intracellular biocatalysis. The porous shell can protect the encapsulated enzymes against proteolysis and attenuate immunological response. We developed a microemulsion-templating method for confining horseradish peroxidase (HRP) in the cavity of HSN.

Enhanced non-endocytotic uptake of mesoporous silica nanoparticles by shortening the peptide transporter arginine side chain.

Mesoporous silica nanoparticles (MSNs) are multifunctional nanocarriers with potential biomedical applications. However, MSNs are frequently trapped in endosomes upon cellular uptake through endocytosis, requiring endosomal escape. Herein, enhanced nonendocytosis was observed for 300 nm MSNs by conjugating peptides with noncanonical arginine analogs.

A broad range fluorescent pH sensor based on hollow mesoporous silica nanoparticles, utilising the surface curvature effect.

In this study, a broad range pH sensor was synthesized by loading the pH sensitive dye, fluorescein isothiocyanate (FITC), and a reference dye, rhodamine B isothiocyanate (RITC), into the mesostructure of hollow mesoporous silica nanoparticles (HMSNs) synthesized using a co-condensation method. Compared to a pH sensor based on the same pair of dyes on conventional mesoporous silica nanoparticles (MSNs), this dual-labeled pH sensor based on HMSNs shows a larger pH sensitive range, between 4.5 and 8.

A simple plant gene delivery system using mesoporous silica nanoparticles as carriers.

A facile DNA delivery method would greatly facilitate studies of plant functional genomics. However, plant cell walls limit the utilization of nanoparticles on plant research. Here, we employed functionalized mesoporous silica nanoparticles (MSNs) to develop a MSN-mediated plant transient gene expression system.

Nonviral cell labeling and differentiation agent for induced pluripotent stem cells based on mesoporous silica nanoparticles.

The generation of induced pluripotent stem cells (iPSCs) is an innovative personalized-regenerative technology, which can transform own-self somatic cells into embryonic stem (ES)-like cells, which have the potential to differentiate into all cell types of three dermal lineages. However, how to quickly, efficiently, and safely produce specific-lineage differentiation from pluripotent-state cells and iPSCs is still an open question. The objective of the present study was to develop a platform of a nonviral gene delivery system of mesoporous silica nanoparticles (MSNs) to rapidly generate iPSC-derived definitive-lineage cells, including endodermal-differentiated cells.

Manganese-enhanced MRI of rat brain based on slow cerebral delivery of manganese(II) with silica-encapsulated Mn x Fe(1-x) O nanoparticles.

In this work, we report a monodisperse bifunctional nanoparticle system, MIO@SiO2 -RITC, as an MRI contrast agent [core, manganese iron oxide (MIO); shell, amorphous silica conjugated with rhodamine B isothiocyanate (RITC)]. It was prepared by thermal decomposition and modified microemulsion methods. The nanoparticles with varying iron to manganese ratios displayed different saturated magnetizations and relaxivities.

High payload Gd(iii) encapsulated in hollow silica nanospheres for high resolution magnetic resonance imaging.

For clear MR imaging of blood vessels, a long blood circulation time of effective T contrast agents is necessary. Nanoparticulate MR contrast agents are much more effective owing to their enhanced relaxivity, a result of reduced tumbling rates, and large payloads of active magnetic species. PEGylated yolk-shell silica nanospheres containing high payloads of Gd(iii) with cross-linking ligands are synthesized and evaluated as a blood-pool magnetic resonance contrast agent.

A new strategy for intracellular delivery of enzyme using mesoporous silica nanoparticles: superoxide dismutase.

We developed mesoporous silica nanoparticle (MSN) as a multifunctional vehicle for enzyme delivery. Enhanced transmembrane delivery of a superoxide dismutase (SOD) enzyme embedded in MSN was demonstrated. Conjugation of the cell-penetrating peptide derived from the human immunodeficiency virus 1 (HIV) transactivator protein (TAT) to mesoporous silica nanoparticle is shown to be an effective way to enhance transmembrane delivery of nanoparticles for intracellular and molecular therapy.

Integrated nanophotonic hubs based on ZnO-Tb(OH)3/SiO2 nanocomposites.

Optical integration is essential for practical application, but it remains unexplored for nanoscale devices. A newly designed nanocomposite based on ZnO semiconductor nanowires and Tb(OH)3/SiO2 core/shell nanospheres has been synthesized and studied. The unique sea urchin-type morphology, bright and sharply visible emission bands of lanthanide, and large aspect ratio of ZnO crystalline nanotips make this novel composite an excellent signal receiver, waveguide, and emitter.

PEGylated silica nanoparticles encapsulating multiple magnetite nanocrystals for high-performance microscopic magnetic resonance angiography.

A novel magnetic resonance (MR) angiographic method, 3DΔR2-mMRA (three dimensional and ΔR2 based microscopy magnetic resonance angiography), is developed as a clinical diagnosis for depicting the function and structure of cerebral small vessels. However, the visibility of microvasculatures and the precision of cerebral blood volume calculation greatly rely on the transverse relaxivity and intravascular half-life of contrast agent, respectively. In this work, we report a blood pool contrast agent named H-Fe₃O₄@SiO₂-PEG where multiple Fe₃O₄ nanocrystals are encapsulated in a thin silica shell to enhance the T₂-relaxivity (r₂ = 342.

Mesoporous silica nanoparticles as nanocarriers.

Modern nanomedicine aims at delivering drugs or cells specifically to defective cells; therefore, this calls for developing multifunctional nanocarriers for drug delivery and cell-tracking. Mesoporous silica nanoparticles (MSNs) are well suited for this task. In this feature article, we highlight the strategies in the synthesis and functionalization of small, uniform and colloidal stable MSNs.

Uniform mesoporous silica hexagon and its two-dimensional colloidal crystal.

Well-ordered mesoporous silica nanoparticles with uniform hexagonal disk shapes are synthesized under dilute alkaline conditions with a two-step process, separating the nucleation and growth process. The resulting monodisperse hexagons can be arranged in a 2-dimensional (2D) ordered periodical super-structure. The hexagonal symmetry is similar in both scales.

Synthesis of hollow silica nanospheres with a microemulsion as the template.

We demonstrate a sol-gel approach, using a water-in-oil microemulsion as the template, for the synthesis of hollow and yolk/shell silica nanospheres, which can encapsulate pre-formed hydrophobic nanoparticles, and we then explore these multifunctional hollow nanospheres in cell-labeling applications.

Mesoporous silica nanoparticles as a delivery system of gadolinium for effective human stem cell tracking.

The progress of using gadolinium (Gd)-based nanoparticles in cellular tracking lags behind that of superparamagnetic iron oxide (SPIO) nanoparticles in magnetic resonance imaging (MRI). Here, dual functional Gd-fluorescein isothiocyanate mesoporous silica nanoparticles (Gd-Dye@MSN) that possess green fluorescence and paramagnetism are developed in order to evaluate their potential as effective T1-enhancing trackers for human mesenchymal stem cells (hMSCs). hMSCs are labeled efficiently with Gd-Dye@MSN via endocytosis.

Internalization of mesoporous silica nanoparticles induces transient but not sufficient osteogenic signals in human mesenchymal stem cells.

The biocompatibility of nanoparticles is the prerequisite for their applications in biomedicine but can be misleading due to the absence of criteria for evaluating the safety and toxicity of those nanomaterials. Recent studies indicate that mesoporous silica nanoparticles (MSNs) can easily internalize into human mesenchymal stem cells (hMSCs) without apparent deleterious effects on cellular growth or differentiation, and hence are emerging as an ideal stem cell labeling agent. The objective of this study was to thoroughly investigate the effect of MSNs on osteogenesis induction and to examine their biocompatibility in hMSCs.

Mesoporous silica nanoparticles improve magnetic labeling efficiency in human stem cells.

Tumblerlike magnetic/fluorescein isothiocyanate (FITC)-labeled mesoporous silica nanoparticles, Mag-Dye@MSNs, have been developed, which are composed of silica-coated core-shell superparamagnetic iron oxide (SPIO@SiO(2)) nanoparticles co-condensed with FITC-incorporated mesoporous silica. Mag-Dye@MSNs can label human mesenchymal stem cells (hMSCs) through endocytosis efficiently for magnetic resonance imaging (MRI) in vitro and in vivo, as manifested by using a clinical 1.5-T MRI system with requirements of simultaneous low incubation dosage of iron, low detection cell numbers, and short incubation time.

The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells.

Cellular uptake of nanoparticles for stem cell labeling/tracking is considered as the most promising method. Recently mesoporous silica nanoparticles (MSNs) are emerging as an idea agent for efficient stem cell labeling. The objective of this study was to evaluate the effect of surface charge on the highly efficient cellular uptake and in vitro cytotoxicity of MSNs in human mesenchymal stem cells (hMSCs).

Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling.

A superparamagnetic iron oxide (SPIO) nanoparticle is emerging as an ideal probe for noninvasive cell tracking. However, its low intracellular labeling efficiency has limited the potential usage and has evoked great interest in developing new labeling strategies. We have developed fluorescein isothiocyanate (FITC)-incorporated silica-coated core-shell SPIO nanoparticles, SPIO@SiO2(FITC), with diameters of 50 nm, as a bifunctionally magnetic vector that can efficiently label human mesenchymal stem cells (hMSCs), via clathrin- and actin-dependent endocytosis with subsequent intracellular localization in late endosomes/lysosomes.

Highly efficient cellular labeling of mesoporous nanoparticles in human mesenchymal stem cells: implication for stem cell tracking.

Tracking the distribution of stem cells is crucial to their therapeutic use. However, the usage of current vectors in cellular labeling is restricted by their low internalizing efficiency. Here, we reported a cellular labeling approach with a novel vector composed of mesoporous silica nanoparticles (MSNs) conjugated with fluorescein isothiocyanate in human bone marrow mesenchymal stem cells and 3T3-L1 cells, and the mechanism about fluorescein isothiocyanate-conjugated MSNs (FITC-MSNs) internalization was studied.