Efficient MRI labeling of endothelial progenitor cells: Design of thiolated surface stabilized superparamagnetic iron oxide nanoparticles

The aim of this study was to design thiolated surface stabilized superparamagnetic iron oxide nanoparticles (TSS-SPIONs) for efficient internalization with high MRI sensitivity. TSS-SPIONs were developed by chelation between thiolated chitosan–thioglycolic acid (chitosan–TGA) hydrogel and iron ions (Fe2+/Fe3+). Likely, unmodified chitosan hydrogel SPIONs (UC-SPIONs) and uncoated SPIONs were used as control. Moreover, TSS-SPIONs were investigated regarding to their iron core size, hydrodynamic diameter, zeta potential, iron contents, molar relaxivities (r1 and r2), and cellular internalization. TSS-SPIONs demonstrated an iron oxide core diameter (crystallite size by XRD) of 3.1 ± 0.02 nm, a hydrodynamic diameter of 94 ± 20 nm, a zeta potential of +21 ± 5 mV, and an iron content of 3.6 ± 0.9 mg/mL. In addition, internalization of TSS-SPIONs into human endothelial progenitor cells (EPC) from umbilical cord blood was more than threefold and 17-fold higher in contrast to UC-SPIONs and SPIONs, respectively. With twofold lower incubation iron concentration of TSS-SPIONs, more than threefold higher internalization was achieved as compared to Resovist®. Also, cell viability of more than 90% was observed in the presence of TSS-SPIONs after 24 h. The molar MR relaxivities (r2) value at 1.5 T was threefold higher than that of Resovist® and demonstrated that TSS-SPIONs have the potential as very effective T2 contrast-enhancement agent. According to these findings, TSS-SPIONs with efficient internalization, lower cytotoxicity, and high MRI sensitivity seem to be promising for cell tracking.

Graphical abstractSchematic presentation for the internalization [A] of thiolated surface stabilized superparamagnetic iron oxide nanoparticles [TSS-SPIONs] and MRI signal enhancement [B] for cell tracking [(I): Microscopic images after TSS-SPIONs internalization; (II): High contrast TEM image with iron distribution; (III): ESI-TEM image for net iron distribution].Figure optionsDownload full-size imageDownload high-quality image (143 K)Download as PowerPoint slide