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.

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Go for gold: As‐prepared insulin–Au nanoclusters (NCs) show intense red fluorescence, excellent biocompatibility, and preservation of natural insulin bioactivity in lowering the blood‐glucose level. Their versatility in applications is demonstrated by fluorescence imaging, X‐ray computed tomography, and insulin–inhibitor interactions (see picture; IDE=insulin‐degrading enzyme).

Cells have many advantages as therapeutic agents. They are able to carry out complex functions, as in stem cell [1] or immune cell therapy. [2] For effective therapy, the delivered cells must carry long-lived tracking agents for monitoring the position and fate of the injected cells. At present, monitoring is often carried out by slow histological analysis, which requires tissue biopsy. Recently, the development of noninvasive real-time tracking of injected cells has attracted a lot of attention for its clinical potential. Fluorescent nanomaterials have been successfully utilized as labels in biological and medical applications for imaging [3,4] and diagnostic purposes. [5][6][7] The limited capability of the fluorescence technique in detecting deep tissues restricts the collection of information in vivo. Magnetic resonance imaging (MRI), one of the most important noninvasive imaging techniques, has been widely used for clinical diagnosis [8] and biomedical research. However, its sensitivity is relatively low for cellularlevel applications. [9] Hence, the synthesis of a new MRI con-trast agent [10][11][12][13] with high sensitivity would be of great interest.Recently, the development of a nanomaterial-based probe with multifunctionalities has become a very active field. Preferably, the functionalities should combine the advantages of MRI in noninvasiveness, fluorescence in high sensitivity and resolution, a surface functional group for targeting, and the ability to deliver drugs locally. Among these, the carrying of good and long-lived MRI contrast agents would be the most useful. Our interest is in developing a nanoparticle form of mesoporous silica, which has some unique properties, such as rigid structure, large pore volume, uniform pore size, great surface-modification capability, [14] and good biocompatibility. It has also been demonstrated as a biomarker [15,16] and a drug carrier. [17][18][19] Previously, we reported multimodal tumblerlike mesoporous silica, which carries a magnetic iron oxide nanoparticle as a T 2 contrast agent (T 1 and T 2 = magnetic relaxation times) and a fluorescent dye. [20] However, the T 2 agent often gives poor contrast in dark areas, such as the liver. Herein, we report a new multifunctional mesoporous silica nanorod that possesses green fluorescence and paramagnetism, and could serve as a good contrast agent in T 1 and T 2 imaging.The multimodality of nanoparticle-based monitoring agents has been developed before. However, very few have been demonstrated as a platform in cell monitoring. [21] There are several different combinations of luminescent materials, MRI contrast agents, and support. The iron oxide nanoparticle, a typical T 2 contrast agent, has been demonstrated to be a multimodal probe by surface functionalization with Cy5.5 dye and chlorotoxin to detect gliomas. [22] Santra and co-workers also developed novel multifunctional probes by encapsulating Gd-TSPETE (n-trimethoxysilylpropyl)ethyldiamine triacetic acid trisodium salt) and CdSe:Mn/ZnS core-shell quantum dots o...

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. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes, osteocytes, and chondrocytes, which can still be readily MRI detected. Imaging, with a clinical 1.5-T MRI system and a low incubation dosage of Gd, low detection cell numbers, and short incubation times is demonstrated on both loaded cells and hMSC-injected mouse brains. This study shows that the advantages of biocompatibility, durability, high internalizing efficiency, and pore architecture make MSNs an ideal vector of T1-agent for stem-cell tracking with MRI.