The size of it: Mesoporous silica nanoparticles (MSNs) of controlled size in the range 30 to 280 nm are obtained by adjusting the pH of the reaction solution. The uptake of fluorescein‐labeled MSNs (green, see image) by HeLa cells is size‐dependent, with maximum uptake at a nanoparticle size of 50 nm.

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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. The uptake process displays a time- and dose-dependent behavior. In our system, SPIO@SiO2(FITC) nanoparticles induce sufficient cell MRI contrast at an incubation dosage as low as 0.5 microg of iron/mL of culture medium with 1.2x105 hMSCs, and the in vitro detection threshold of cell number is about 1x104 cells. Furthermore, 1.2x105 labeled cells can also be MRI-detected in a subcutaneous model in vivo. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes and osteocytes which can still be readily MRI detected. This is the first report that hMSCs can be efficiently labeled with MRI contrast nanoparticles and can be monitored in vitro and in vivo with a clinical 1.5-T MRI imager under low incubation concentration of iron oxide, short incubation time, and low detection cell numbers at the same time.

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.

We demonstrate a strategy for the synthesis of multifunctional mesoporous silica nanoparticles. These uniform tumblerlike nanocomposites, which simultaneously possess magnetic, luminescent, and porous properties, have great potential in biomedical applications.

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. FITC-MSNs were efficiently internalized into mesenchymal stem cells and 3T3-L1 cells even in short-term incubation. The process displayed a time- and concentration-dependent manner and was dependent on clathrin-mediated endocytosis. In addition, clathrin-dependent endocytosis seemed to play a decisive role on more internalization and longer stay of FITC-MSNs in mesenchymal stem cells than in 3T3-L1 cells. The internalization of FITC-MSNs did not affect the cell viability, proliferation, immunophenotype, and differentiation potential of mesenchymal stem cells, and 3T3-L1 cells. Finally, FITC-MSNs could escape from endolysosomal vesicles and were retained the architectonic integrity after internalization. We conclude that the advantages of biocompatibility, durability, and higher efficiency in internalization suit MSNs to be a better vector for stem cell tracking than others currently used.

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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.