Division of Radiation Biomedical Research, Korea Institute of Radiological and Medical Sciences, Seoul, 01812, South Korea.
Radiological and Medico-Oncological Sciences, University of Science and Technology, Daejeon, 34113, South Korea.
Sci Rep. 2020 Feb 13;10(1):2560. doi: 10.1038/s41598-020-59445-x.
Although tumour-treating fields (TTFields) is a promising physical treatment modality based on disruption of dipole alignments and generation of dielectrophoretic forces during cytokinesis, not much is known about TTFields-responsive sensitisers. Here, we report a novel TTFields-responsive sensitiser, barium titanate nanoparticles (BTNPs), which exhibit cytocompatibility, with non-cytotoxic effects on breast cancer cells. BTNPs are characterised by high dielectric constant values and ferroelectric properties. Notably, we found that BTNPs sensitised TTFields-resistant breast cancer cells in response to TTFields. In addition, BTNPs accumulated in the cytoplasm of cancer cells in response to TTFields. Further, we showed that TTFields combined with BTNPs exhibited antitumor activity by modulating several cancer-related pathways in general, and the cell cycle-related apoptosis pathway in particular. Therefore, our data suggest that BTNPs increase the antitumor action of TTFields by an electric field-responsive cytosolic accumulation, establishing BTNP as a TTFields-responsive sensitiser.
虽然肿瘤治疗电场（TTFields）是一种很有前途的物理治疗模式，基于有丝分裂过程中偶极子排列的破坏和介电泳力的产生，但对于 TTFields 反应性增敏剂知之甚少。在这里，我们报告了一种新型的 TTFields 反应性增敏剂，钛酸钡纳米颗粒（BTNPs），具有细胞相容性，对乳腺癌细胞没有细胞毒性作用。BTNPs 的特点是具有高介电常数值和铁电特性。值得注意的是，我们发现 BTNPs 可响应 TTFields 增敏 TTFields 耐药乳腺癌细胞。此外，BTNPs 可响应 TTFields 在癌细胞的细胞质中积累。此外，我们表明，TTFields 结合 BTNPs 通过调节几种与癌症相关的途径，特别是细胞周期相关的凋亡途径，表现出抗肿瘤活性。因此，我们的数据表明，BTNPs 通过电场响应的细胞质积累增加 TTFields 的抗肿瘤作用，确立了 BTNP 作为 TTFields 反应性增敏剂。
