Combination of transfection agents and magnetic resonance contrast agents for cellular imaging: relationship between relaxivities, electrostatic forces, and chemical composition.

The purpose of this study was to investigate the changes in electrostatic and magnetic resonance (MR) properties observed when MR contrast agents (CAs) (Feridex, MION-46L, or G5-dendrimer-DOTA-Gd) are combined with transfection agents (TAs) under various conditions for use as a CA-TA complex basis for cellular labeling and MRI. CAs were incubated with various classes of TAs for 0-48 hr in solutions of varying concentrations and pH values. NMR relaxation rates (1/T(1), 1/T(2)), MRI and zeta potential (ZP) of CA-TA solutions were measured. TAs decreased the 1/T(1) and 1/T(2) of G5-DOTA-Gd, Feridex, and MION-46L by 0-95%. Altering the pH of G5-DOTA-Gd-TA decreased the T(1)-weighted signal intensity (SI) on MRI from 0 to 78%. Measured ZP values for G5-DOTA-Gd, Feridex, and MION-46L were -51, -41, and -2.0 mV, respectively. The TA LV had a negative ZP, while the other TAs had ZPs ranging from +20 to +65 mV. The alteration of the ZP and NMR relaxivities of the MR CAs, Feridex, MION-46L, and G5-DOTA-Gd by TAs has been demonstrated. These results enhance our understanding of the relationship between electrostatic and MR properties.

Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells.

Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 microg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for beta-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.