Bifunctional Magnetic Silica\nNanoparticles for Highly Efficient\nHuman Stem Cell Labeling

Abstract

A superparamagnetic iron oxide (SPIO) nanoparticle is emerging as an ideal probe for noninvasive cell tracking. However, its low intracellular\nlabeling efficiency has limited the potential usage and has evoked great interest in developing new labeling strategies. We have developed\nfluorescein isothiocyanate (FITC)-incorporated silica-coated core−shell SPIO nanoparticles, SPIO@SiO₂(FITC), with diameters of 50 nm, as a\nbifunctionally magnetic vector that can efficiently label human mesenchymal stem cells (hMSCs), via clathrin- and actin-dependent endocytosis\nwith subsequent intracellular localization in late endosomes/lysosomes. The uptake process displays a time- and dose-dependent behavior.\nIn 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\nculture 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\ncells can also be MRI-detected in a subcutaneous model in vivo. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation\ncapacities into adipocytes and osteocytes which can still be readily MRI detected. This is the first report that hMSCs can be efficiently labeled\nwith MRI contrast nanoparticles and can be monitored in vitro and in vivo with a clinical 1.5-T MRI imager under low incubation concentration\nof iron oxide, short incubation time, and low detection cell numbers at the same time.