Kang Y J, Kuo C-F, Majd S
Annu Int Conf IEEE Eng Med Biol Soc. 2017 Jul;2017:309-312. doi: 10.1109/EMBC.2017.8036824.
This paper describes the preparation and characterization of polymeric nanoparticles loaded with a potent anti-tumor metal chelator, Di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) for delivery to cancer cells. Metal chelators have been increasingly studied for their anti-cancer properties that rely on the high demand of neoplastic cells for iron. Dp44mT has previously shown great antiproliferative characteristics in several cancers including breast cancer and melanoma. To further expand the application of this highly cytotoxic agent for cancer treatment and to enable its specific delivery to malignant cells, here we apply nano-scale particles (NPs) of biodegradable poly(lactic-co-glycolide) (PLGA) for encapsulation of Dp44mT and evaluate its effectiveness in vitro. The results demonstrated that Dp44mT was efficiently encapsulated in PLGA particles. Resulting NPs were uniform in size and shape and had good colloidal stability. Moreover, Dp44mT encapsulation in PLGA enhanced the water solubility of this agent. Lastly, the present formulation showed high level of cytotoxicity in glioma cells. Together, these results show the potential of PLGA NPs as a nano-carrier for Dp44mT with no apparent impact on the anti-tumor activity of this compound.
本文描述了负载强效抗肿瘤金属螯合剂二 - 2 - 吡啶基甲酮 - 4,4 - 二甲基 - 3 - 硫代半卡巴腙（Dp44mT）的聚合物纳米颗粒的制备及其特性，该纳米颗粒用于递送至癌细胞。金属螯合剂因其抗癌特性而受到越来越多的研究，这些特性依赖于肿瘤细胞对铁的高需求。Dp44mT此前已在包括乳腺癌和黑色素瘤在内的多种癌症中显示出强大的抗增殖特性。为了进一步扩大这种高细胞毒性药物在癌症治疗中的应用，并使其能够特异性递送至恶性细胞，我们在此应用可生物降解的聚乳酸 - 乙醇酸共聚物（PLGA）纳米颗粒来包裹Dp44mT，并评估其体外有效性。结果表明，Dp44mT被有效地包裹在PLGA颗粒中。所得纳米颗粒的大小和形状均匀，具有良好的胶体稳定性。此外，Dp44mT包裹在PLGA中提高了该药物的水溶性。最后，本制剂在胶质瘤细胞中显示出高水平的细胞毒性。总之，这些结果表明PLGA纳米颗粒作为Dp44mT的纳米载体具有潜力，且对该化合物的抗肿瘤活性没有明显影响。
