Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Analyst. 2021 May 21;146(10):3225-3233. doi: 10.1039/d0an02013c. Epub 2021 Apr 8.
One of the best strategies to circumvent drug resistance is the employment of nanocarriers. For the current study, we have employed a nanoemulsion formulation of paclitaxel (PTX) to bypass drug resistance in the MDA-MB-231 cell line and impedance sensing biosensors to determine the exact time that PTX-NE induced apoptosis. Our MTT results demonstrated that PTX treatment could not reduce MDA-MB-231 cell viability to IC even after three days. However, the employment of the reagent TPGS (inhibitor of drug resistance) combined with paclitaxel could partially obviate PTX resistance. Next, the nanoemulsion form of PTX (PTX-NE) was fabricated employing the essential oil of the Satureja khuzestanica plant and was characterized using DLS and TEM methods. Our data showed that after 72 hours, PTX-NE at 250 nM concentration could induce a 50% reduction in cell viability. Moreover, annexin/PI and cell cycle analysis confirmed the apoptotic effect of PTX-NE on cancer cells. Lastly, we measured the impedance of MDA-MB-231 cells treated with the free and nanoemulsion forms of PTX. A significant decrease in the mean impedance of PTX-NE treated cells could be observed after 40 hours. To conclude, we have demonstrated here that PTX-NE could circumvent resistance and induce apoptosis in PTX-resistant breast cancer cells, which could be inferred from their impedance measurement.
规避耐药性的最佳策略之一是使用纳米载体。在本研究中,我们采用了紫杉醇(PTX)的纳米乳剂制剂,以绕过 MDA-MB-231 细胞系的耐药性,并使用阻抗感应生物传感器来确定 PTX-NE 诱导细胞凋亡的确切时间。我们的 MTT 结果表明,PTX 处理甚至在三天后也不能将 MDA-MB-231 细胞活力降低到 IC。然而,使用 TPGS(耐药抑制剂)与紫杉醇联合使用可以部分克服 PTX 耐药性。接下来,我们采用 Satureja khuzestanica 植物精油制备了 PTX 的纳米乳剂(PTX-NE),并采用 DLS 和 TEM 方法对其进行了表征。我们的数据表明,在 72 小时后,浓度为 250 nM 的 PTX-NE 可以将细胞活力降低 50%。此外, annexin/PI 和细胞周期分析证实了 PTX-NE 对癌细胞的凋亡作用。最后,我们测量了用游离和纳米乳剂形式的 PTX 处理的 MDA-MB-231 细胞的阻抗。可以观察到,在用 PTX-NE 处理的细胞中,平均阻抗在 40 小时后显著下降。总之,我们在这里证明了 PTX-NE 可以绕过耐药性并诱导 PTX 耐药乳腺癌细胞凋亡,这可以从它们的阻抗测量中推断出来。