Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland ; Wroclaw Research Centre EIT+, Wroclaw, Poland.
Department of Protein Engineering, Faculty of Biotechnology, University of Wroclaw, Wroclaw, Poland.
Int J Nanomedicine. 2014;9:67-76. doi: 10.2147/IJN.S52539. Epub 2013 Dec 18.
Targeted therapy is a method owing to its limited side effect profile, particularly in cancer treatment. Magnetic hyperthermia, which is induced by nanoparticles (NPs) conjugated with targeting agents, can be useful in combination with chemo- or radiotherapy. In this paper, we constructed dextran-coated ferric oxide NPs conjugated with specific anti-human epidermal growth factor receptor (HER2) aptamer and used them to induce magnetic hyperthermia in cultured cells. The specificity of the tagged NPs was determined by studying their effect relative to that of non-tagged NPs against two cell lines: human adenocarcinoma SK-BR3, overexpressing the HER2 receptor; and U-87 MG, a human glioblastoma epithelial cell line, not expressing HER2. In order to confirm the interaction of the tagged NPs with the cells we used, fluorescence microscopy and fluorescence-activated cell sorting analysis were performed. All of these experiments showed that the aptamer-tagged NPs were highly specific toward the HER2-expressing cells. In addition, a ninetyfold lower dose of the tagged NPs relative to that of the non-tagged NPs was needed to achieve ~50% cell killing by hyperthermia of the SK-BR3 cell line, while for the U-87 MG cells the viability level was close to 100%. These results show that targeted NPs can be applied at substantially lower doses than non-targeted ones to achieve similar effects of hyperthermia, which should greatly limit the side effects of treatment.
靶向治疗因其副作用谱有限而受到关注,尤其是在癌症治疗中。与化疗或放疗联合使用与靶向剂偶联的纳米颗粒(NPs)诱导的磁热疗可能很有用。在本文中,我们构建了与特定抗人表皮生长因子受体(HER2)适体偶联的葡聚糖包覆的氧化铁 NPs,并将其用于诱导培养细胞中的磁热疗。通过研究标记的 NPs 相对于未标记的 NPs 对两种细胞系(过表达 HER2 受体的人腺癌 SK-BR3 和不表达 HER2 的人神经胶质瘤上皮细胞系 U-87 MG)的作用,确定了标记的 NPs 的特异性。为了确认标记的 NPs 与我们所用细胞的相互作用,进行了荧光显微镜和荧光激活细胞分选分析。所有这些实验都表明,适体标记的 NPs 对表达 HER2 的细胞具有高度特异性。此外,与未标记的 NPs 相比,标记的 NPs 只需约 90 倍的低剂量即可通过 SK-BR3 细胞系的热疗达到约 50%的细胞杀伤,而对于 U-87 MG 细胞,存活率接近 100%。这些结果表明,与非靶向 NPs 相比,靶向 NPs 可以以更低的剂量应用,以达到类似的热疗效果,这应大大限制治疗的副作用。