Department of Radiology, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat‑Sen University, Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, Guangdong 510055, P.R. China.
Department of Radiology, The First Affiliated Hospital, Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7597-7602. doi: 10.3892/mmr.2017.7565. Epub 2017 Sep 20.
The aim of the present study was to investigate the feasibility of using folate‑targeted superparamagnetic iron oxide nanoparticles (SPIO) as a magnetic resonance (MR) contrast agent that targets human tongue cancer cells. Folate‑targeted and folate‑free bilayer micelles composed of a diblock copolymer of polyethylene glycol (PEG) and poly‑caprolactone (PCL) that encapsulated SPIO in their hydrophobic core (SPIO‑PEG‑PCL micelles) were synthesized. The cytotoxicity of each set of micelles towards Tca‑8113 cells was examined using methyl thiazolyl tetrazolium (MTT) assays. Tca‑8113 cells were incubated with folate‑free SPIO‑PEG‑PCL micelles and folate‑targeted SPIO‑PEG‑PCL micelles at an Fe concentration of 80 µg/ml for 0.5, 1 and 2 h. MR imaging was subsequently performed and relative T2 relaxation time was recorded. Endocytosis of each micelle type was observed using Prussian blue staining. The MTT assays demonstrated that varying concentrations of folate‑targeted SPIO‑PEG‑PCL micelles did not result in statistically significant differences in Tca‑8113 cell viability when compared with folate‑free SPIO‑PEG‑PCL micelles (F=0.698; P=0.676). In the MR images obtained, decreased T2‑weighted signal intensity was observed for the folate‑targeted SPIO‑PEG‑PCL and folate‑free SPIO‑PEG‑PCL micelle treatments, particularly after the 2‑h incubation period. However, the folate‑targeted micelles exhibited a significantly greater decrease in signal intensity and a higher relative T2 relaxation time at each time point (P=0.002). In addition, blue intracellular particles were observed in the cells that were incubated with each type of micelle and stained with Prussian blue. However, a greater number of blue particles underwent endocytosis in the folate‑targeted group. Thus, folate‑targeted SPIO‑PEG‑PCL micelles exhibited preferential targeting of Tca‑8113 cells when compared with folate‑free SPIO‑PEG‑PCL micelles, and these results support the potential for these micelles to be used for the early diagnosis of tongue cancer.
本研究旨在探讨叶酸靶向超顺磁性氧化铁纳米粒子(SPIO)作为磁共振(MR)对比剂靶向人舌癌细胞的可行性。合成了由聚乙二醇(PEG)和聚己内酯(PCL)嵌段共聚物组成的叶酸靶向和无叶酸双层胶束,其疏水性核中包裹 SPIO(SPIO-PEG-PCL 胶束)。使用噻唑蓝(MTT)测定法检查每组胶束对 Tca-8113 细胞的细胞毒性。将 Tca-8113 细胞在 80μg/ml 的 Fe 浓度下与无叶酸 SPIO-PEG-PCL 胶束和叶酸靶向 SPIO-PEG-PCL 胶束孵育 0.5、1 和 2 h。随后进行 MR 成像并记录相对 T2 弛豫时间。使用普鲁士蓝染色观察每种胶束类型的内吞作用。MTT 测定表明,与无叶酸 SPIO-PEG-PCL 胶束相比,不同浓度的叶酸靶向 SPIO-PEG-PCL 胶束对 Tca-8113 细胞活力没有统计学上的显著差异(F=0.698;P=0.676)。在获得的 MR 图像中,观察到叶酸靶向 SPIO-PEG-PCL 和无叶酸 SPIO-PEG-PCL 胶束处理后 T2 加权信号强度降低,特别是在 2 h 孵育后。然而,叶酸靶向胶束在每个时间点的信号强度降低和相对 T2 弛豫时间均显著更高(P=0.002)。此外,用每种类型的胶束孵育并用普鲁士蓝染色后,观察到细胞内有蓝色的细胞内颗粒。然而,在叶酸靶向组中,更多的蓝色颗粒发生内吞作用。因此,与无叶酸 SPIO-PEG-PCL 胶束相比,叶酸靶向 SPIO-PEG-PCL 胶束对 Tca-8113 细胞具有优先靶向性,这些结果支持这些胶束用于舌癌的早期诊断。
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