Si Han Wu

Size Effect on Cell Uptake in Well‐Suspended, Uniform Mesoporous Silica Nanoparticles

because itdetermines the mechanism and rate of cell uptake of ananoparticle and its ability to permeate through tissue. Theinvestigation of particle size effects will impact on allapplications of nanoparticles in biomedicine. It has beenfoundthatparticlesizecanaffecttheefficiencyandpathwayofcellularuptakebyinfluencingtheadhesionoftheparticlesandtheir interaction with cells.

Synthesis of mesoporous silica nanoparticles

Good control of the morphology, particle size, uniformity and dispersity of mesoporous silica nanoparticles (MSNs) is of increasing importance to their use in catalyst, adsorption, polymer filler, optical devices, bio-imaging, drug delivery, and biomedical applications. This review discusses different synthesis methodologies to prepare well-dispersed MSNs and hollow silica nanoparticles (HSNs) with tunable dimensions ranging from a few to hundreds of nanometers of different mesostructures. The methods include fast self-assembly, soft and hard templating, a modified Stöber method, dissolving-reconstruction and modified aerogel approaches. In practical applications, the MSNs prepared by these methods demonstrate good potential for use in high-performance catalysis, antireflection coating, transparent polymer-MSNs nanocomposites, drug-release and theranostic systems.

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. We then discuss cell uptake of MSNs and tracking cells, as both aspects are closely related to the efficacy of drug delivery and theranostics. Some examples of stimulated drug delivery are described. For application considerations, toxicity and pharmacokinetics are critical issues and in vivo studies are summarized.

Multifunctional mesoporous silica nanoparticles for intracellular labeling and animal magnetic resonance imaging studies

The unique properties of mesoporous silica nanoparticles (MSNs), such as high surface areas, uniform pore size, easy modification, and biocompatibility, make them highly suitable for biological applications. In previous reports, MSNs have been demonstrated to function as cell markers and as gene transfection and drug delivery agents. Although these cell-level studies are attractive, some important issues, such as the cellular uptake efficiency, toxicity, and circulation behavior of MSNs in living animals, still have to be addressed for further practical animal-level applications. Superparamagnetic nanoparticles (i.e. , magnetite) with diameters of less than 20 nm exhibit effective magnetic resonance imaging (MRI) contrast enhancement behavior. Because MRI is a noninvasive imaging method, it is a powerful tool with which to track the migration of cells and to investigate the distribution of nanoparticles in the living body. The main drawbacks of the MRI technique, however, are low sensitivity and resolution, which make it unable to provide detailed biological information. In previous reports, magnetic–optical bifunctional nanoparticles have been fabricated for imaging applications. However, they are nonporous hybrid magnetic composites. To offset the shortcomings and to expand the bioimaging/delivery ACHTUNGTRENNUNGapplications, simultaneous attachment of a fluorescent probe (subcellular imaging) and a MRI probe (noninvasive imaging) to MSN is an important task. Recently, we adopted a strategy involving the simultaneous fusion of amorphous silica shells of Fe3O4@SiO2 nanoparticles with MSNs that are attached to fluorescein isothiocyanate (FITC). These nanoparticles with multifunctionalities—fluorescent, magnetic, and porous (MagDye@MSNs)—can simultaneously serve as bimodal imaging probes and drug reservoirs. Thus, we believe that MagDye@MSNs would be a suitable material with which to study the cellular uptake efficiency, toxicity, and accumulative behavior of MSNs in living animals. To the best of our knowledge, this is the first report of direct injection of mesoporous silica nanoparticles (MSNs) into mice and of in vivo visualization of the localization of MSNs by MRI. Mag-Dye@MSNs were synthesized according to the method we previously developed (the detailed synthetic method is described in the Experimental Section). A transmission electron microscopy (TEM) image of the Mag-Dye@MSNs (Figure 1)

Catalytic nano-rattle of Au@hollow silica: towards a poison-resistant nanocatalyst

In this work, size-controlled gold nanocatalysts (2.8 to 4.5 nm) inside monodisperse hollow silica nanospheres, Au@HSNs, have been prepared by using a water-in-oil microemulsion as a template. The size of gold nanocatalysts can be easily controlled based on the gold precursor and the chloroauric acid concentration used during synthesis. These Au@HSN nanocatalysts were characterized by transmission electron microscopy, scanning electron microscopy, N2 adsorption–desorption isotherms, powder X-ray diffraction, and UV-vis spectrometer. Furthermore, we demonstrate their catalytic capability with respect to the 4-nitrophenol reduction reaction in the absence and presence of a thiol compound, meso-2,3-dimercaptosuccinic acid. The results show that the Au@HSNs display highly catalytic activity and resistance to other strongly adsorbing molecules in reaction solutions.

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 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. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes and osteocytes, which can still be readily detected by MRI. Moreover, a higher MRI signal intensity decrease is observed in Mag-Dye@MSN-treated cells than in SPIO@SiO(2)-treated cells. This is the first report that MCM-41-type MSNs are advantageous to cellular uptake, as manifested by a higher labeling efficiency of Mag-Dye@MSNs than SPIO@SiO(2).

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. Uptake of MSNs into hMSCs did not affect the cell viability, proliferation and regular osteogenic differentiation of the cells. However, the internalization of MSNs indeed induced actin polymerization and activated the small GTP-bound protein RhoA. The MSN-induced cellular protein responses as believed to cause osteogenesis of hMSCs did not result in promotion of regular osteogenic differentiation as analyzed by cytochemical stain and protein activity assay of alkaline phosphatase (ALP). When the effect of MSNs on ALP gene expression was further examined by reverse transcriptase polymerase chain reaction, MSN-treated hMSCs were shown to have significantly higher mRNA expression than control cells after 1-hour osteogenic induction. The induction of ALP gene expression by MSNs, however, was absent in cells after 1-day incubation with osteogenic differentiation. Together our results show that the internalization of MSNs had a significant effect on the transient protein response and osteogenic signal in hMSCs, thereby suggesting that the effects of nanoparticles on diverse aspects of cellular activities should be carefully evaluated even though the nanoparticles are generally considered as biocompatible at present.

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 T1 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. The hydrophilic PEG coating and the microporous silica shell allow water exchange while keeping the multi-nuclear Gd species from leaching out. These Gd(iii)-containing yolk-shell silica nanoparticles with PEGylated surfaces give excellent resolution and contrast in magnetic resonance angiography images of vasculature in rat brains.

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 = 342.8 mM⁻¹ s⁻¹) and poly(ethylene glycol) (PEG) is employed to reduce opsonization and prolong circulation time of nanoparticles. Utilization of the newly developed H-Fe₃O₄@SiO₂-PEG with a novel MR angiographic methodology, a high-resolution MR image of rat cerebral microvasculatures is successfully obtained.