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.

中文翻译：

---

超小氧化铁纳米粒子对神经干细胞的细胞摄取，增殖和多能性的表面效应

超小型氧化铁纳米粒子（USIONPs）最近已被开发为T ₂磁共振成像造影剂的标记探针。然而，它们在干细胞追踪中的用途受到限制，特别是作为T ₁造影剂。在这项研究中，我们研究了USIONP表面涂层对已建立的和原代神经干细胞（NSC）的增殖，细胞摄取和多态性的影响。USIONPs用葡萄糖酸（GA），鞣酸（TA）和透明质酸（HA）功能化以标记NSC。所有功能化的USIONP的特征均为T ₁造影剂通过松弛度测量。与GA相比，TA和HA涂层的直接功能化以剂量依赖的方式促进了NSC增殖并增强了细胞摄取。此外，取决于HA分子量，HA涂层在初级NSC中显示出增强的细胞增殖和细胞摄取。干细胞的特征得到了很好的维护，并通过神经球形成以及干和分化标志物的基因表达进行了验证。总的来说，我们证明了使用USIONPs的各种表面包被策略可以增强NSC增殖，细胞摄取和多能性。