Surface Effects of Ultrasmall Iron Oxide Nanoparticles on Cellular Uptake, Proliferation, and Multipotency of Neural Stem Cells

Ultrasmall iron oxide nanoparticles (USIONPs) have been recently developed as labeling probes for T2 magnetic resonance imaging contrast agents. However, their use in stem cell tracking has been limited, especially as T1 contrast agents. In this study, we studied the effects of USIONP surface coatings on proliferation, cellular uptake, and multipontency of established and primary neural stem cells (NSCs). USIONPs were functionalized with gluconic acid (GA), tannic acid (TA), and hyaluronic acid (HA) to label the NSCs. All functionalized USIONPs were characterized as T1 contrast agents via relaxivity measurements. Direct functionalization with TA and HA coating promoted NSC proliferation and enhanced cellular uptake in a dose-dependent manner compared to those with GA. Furthermore, HA coating showed enhanced cell proliferation and cellular uptake in primary NSCs depending on the HA molecular weight. Stem cell characteristics were well-maintained, verified by neurosphere formation and gene expression of stemness and differentiation markers. Collectively, we demonstrated that NSC proliferation, cellular uptake, and multipotency can be enhanced using various surface coating strategies of USIONPs.