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Quantitative intracellular magnetic nanoparticle uptake measured by live cell magnetophoresis

Ying Jing^*,, Niladri Mal, P. Stephen Williams^*, Maritza Mayorga, Marc S. Penn, Jeffrey J. Chalmers and Maciej Zborowski^*,1

^* Department of Biomedical Engineering/ND20, Lerner Research Institute, and

Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio, USA; and

Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, USA

¹ Correspondence: Department of Biomedical Engineering/ND20, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195, USA. E-mail: zborowm{at}ccf.org

Superparamagnetic iron oxide (SPIO) particles have been used successfully as an intracellular contrast agent for nuclear MRI cell tracking in vivo. We present a method of detecting intracellular SPIO colloid uptake in live cells using cell magnetophoresis, with potential applications in measuring intracellular MRI contrast uptake. The method was evaluated by measuring shifts in mean and distribution of the cell magnetophoretic mobility, and the concomitant changes in population frequency of the magnetically positive cells when compared to the unmanipulated negative control. Seven different transfection agent (TA) -SPIO complexes based on dendrimer, lipid, and polyethylenimine compounds were used as test standards, in combination with 3 different cell types: mesenchymal stem cells, cardiac fibroblasts, and cultured KG-1a hematopoietic stem cells. Transfectol (TRA) -SPIO incubation resulted in the highest frequency of magnetically positive cells (>90%), and Fugene 6 (FUG) -SPIO incubation the lowest, below that when using SPIO alone. A highly regular process of cell magnetophoresis was amenable to intracellular iron mass calculations. The results were consistent in all the cell types studied and with other reports. The cell magnetophoresis depends on the presence of high-spin iron species and is therefore expected to be directly related to the cell MRI contrast level.—Jing, Y., Mal, N., Williams, P. S., Mayorga, M., Penn, M. S., Chalmers, J. J., Zborowski, M. Quantitative intracellular magnetic nanoparticle uptake measured by live cell magnetophoresis.

Key Words: intracellular MRI contrast • stem cell tracking • SPIO • transfection agent • intracellular iron • particle tracking velocimetry