Folic acid modified superparamagnetic iron oxide nanocomposites for targeted hepatic carcinoma MR imaging
作者:Zhongling Wang、Jing Zhu、Yinyin Chen、Kaiming Geng、Nong Qian、Liang Cheng、Ziwei Lu、Yue Pan、Liang Guo、Yonggang Li、Hongwei Gu
DOI:10.1039/c3ra45878d
日期:——
A novel targeted MRI contrast agent for tumor cells and tumor over-expressing affinity receptor was synthesized and characterized. Dopamine (DA) was used to present functional molecules on the surface of superparamagnetic iron oxide nanoparticles (SPIONs), and dextran was conjugated with the folic acid (FA) that forms stable nanocomposites. The T2 values of the targeted and non-targeted nanoparticles at 3.0 T were 10.9 ms and 11.8 ms, respectively. The T2 relaxivity values (r2) were 91.7 s−1 mM−1 and 84.7 s−1 mM−1, respectively. The results of the competitive inhibition test suggest that the SPION-DA-dextran-FA uptake is associated with folate receptor binding. In the in vitro study, the T2 signal intensity of hepatic carcinoma cells (Bel 7402) incubated with the folate targeting nanocomposites decreased significantly. In contrast, the T2 signal did not show an obvious decrease for cells treated with the non-targeting nanocomposites. In the in vivo study, the T2 signal decreased significantly 18 hours after injection of the folate targeting contrast agent. In contrast, the maximum intensity of the non-targeting group appeared 0.5–2 hours after injection and the T2 signal intensities recovered gradually 4 hours after injection. Our results indicated that FA targeting SPIONs have the ability for use as a novel targeting MRI contrast agent and have a better targeting tropism to the Bel 7402 cells and tumor.
研究人员合成并鉴定了一种新型肿瘤细胞靶向磁共振成像造影剂和肿瘤过度表达亲和受体。多巴胺(DA)被用于在超顺磁性氧化铁纳米粒子(SPIONs)表面呈现功能分子,右旋糖酐与叶酸(FA)共轭形成稳定的纳米复合材料。靶向纳米粒子和非靶向纳米粒子在 3.0 T 下的 T2 值分别为 10.9 ms 和 11.8 ms。T2弛豫值(r2)分别为 91.7 s-1 mM-1 和 84.7 s-1 mM-1。竞争性抑制试验的结果表明,SPION-DA-葡聚糖-FA 的摄取与叶酸受体结合有关。在体外研究中,与叶酸靶向纳米复合材料培养的肝癌细胞(Bel 7402)的 T2 信号强度显著下降。相比之下,用非靶向纳米复合材料处理的细胞的 T2 信号强度没有明显下降。在体内研究中,注射叶酸靶向造影剂 18 小时后,T2 信号明显下降。相比之下,非靶向组的最大强度出现在注射后 0.5-2 小时,T2 信号强度在注射后 4 小时逐渐恢复。我们的研究结果表明,叶酸靶向 SPIONs 可用作新型靶向磁共振成像造影剂,而且对 Bel 7402 细胞和肿瘤具有更好的靶向滋养性。