Holley C K, Majd S
Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:5029-5032. doi: 10.1109/EMBC44109.2020.9176197.
We have recently reported encapsulating an antitumor iron chelator, Dp44mT (Di-2-pyridylketone-4,4dimethyl-3-thiosemicarbazone), in nanoparticles (NPs) of poly(lactic-co-glycolic acid) (PLGA). In this paper, we examine the effectiveness of this nano-formulation, referred to as Dp44mT-NPs, against several cancer cell lines in vitro; specifically, we evaluate the cytotoxicity of this formulation in glioma (U87, U251), breast (MCF7), and colorectal (HT29) cancer cell lines. Cell viability results from treatment of glioma cells with Dp44mT-NPs for 24-72 hrs revealed that these NPs were highly toxic towards these malignant cells with very low IC values (<100 nM). Although addition of a PEG (poly(ethylene glycol)) layer to the surface of NPs reduced their toxicity in glioma cells, they remained highly toxic towards these cells (IC of 135-210 nM). Dp44mT-NPs were also toxic towards breast MCF7 and colorectal HT29 cells, but at higher dosages (IC >1 µM) compared to glioma cells. Addition of PEG to these NPs, again lowered their toxicity in these cells. Varying the percentage of PEG on NPs resulted in changes in their cytotoxicity, highlighting the necessity of further optimization of this parameter. This study, overall, demonstrates the therapeutic potential of Dp44mT-NPs against different malignant cells, with particularly promising results in highly-aggressive glioma tumor cells.
我们最近报道了将一种抗肿瘤铁螯合剂Dp44mT（二-2-吡啶酮-4,4-二甲基-3-硫代半卡巴腙）包裹于聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NPs）中。在本文中，我们研究了这种被称为Dp44mT-NPs的纳米制剂在体外对几种癌细胞系的有效性；具体而言，我们评估了该制剂在胶质瘤（U87、U251）、乳腺癌（MCF7）和结直肠癌（HT29）细胞系中的细胞毒性。用Dp44mT-NPs处理胶质瘤细胞24至72小时后的细胞活力结果显示，这些纳米颗粒对这些恶性细胞具有高毒性，IC值极低（<100 nM）。尽管在纳米颗粒表面添加聚乙二醇（PEG）层降低了它们在胶质瘤细胞中的毒性，但它们对这些细胞仍具有高毒性（IC为135 - 210 nM）。Dp44mT-NPs对乳腺癌MCF7和结直肠癌HT29细胞也有毒性，但与胶质瘤细胞相比剂量更高（IC>1 μM）。在这些纳米颗粒中添加PEG再次降低了它们在这些细胞中的毒性。改变纳米颗粒上PEG的百分比导致其细胞毒性发生变化，突出了进一步优化该参数的必要性。总体而言，这项研究证明了Dp44mT-NPs对不同恶性细胞的治疗潜力，在高度侵袭性的胶质瘤肿瘤细胞中取得了特别有前景的结果。
