Bifunctional Magnetic Silica Nanoparticles for Highly Efficient Human Stem Cell Labeling

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Abstract
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 μg of iron/mL of culture medium with 1.2 × 105 hMSCs, and the in vitro detection threshold of cell number is about 1 × 104 cells. Furthermore, 1.2 × 105 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.