Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Medical Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
AAPS PharmSciTech. 2020 Jun 5;21(5):166. doi: 10.1208/s12249-020-01710-3.
Our aim in this study was to clarify the combination anticancer effect of Noscapine (Nos) loaded in a polymeric nanocarrier with Doxorubicin (Dox) on breast cancer cells. Nanoprecipitation method was used to prepare methoxy polyethylene glycol (mPEG), poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) containing Nos. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were used to characterize the prepared Nos NPs. The anticancer activity of Nos NPs alone and in combination with Dox was assessed on 4T1 breast cancer cell line and in mice model. Spherical-shaped Nos NPs were prepared, with size of 101 ± 4.80 nm and zeta potential of - 15.40 ± 1 mV. Fourier transform infrared (FTIR) spectroscopy results demonstrated that Nos chemical structure was kept stable during preparation process. However, differential scanning calorimetric (DSC) thermogram proved that crystalline state of Nos changed to amorphous state in Nos NPs. The entrapment efficacy % (EE%) and drug loading % (DL%) of Nos NPs were about 87.20 ± 3.50% and 12.50 ± 2.30%, respectively. Synergistic anticancer effects of Nos both in free form (in hydrochloride form, Nos HCl) and Nos NPs form with Dox hydrochloride (Dox HCl) were observed on 4T1 cells. Combination of Nos NPs and Dox HCl inhibited tumor growth (68.50%) in mice more efficiently than Nos NPs (55.10%) and Dox HCl (32%) alone. Immunohistochemical (IHC) analysis of the tumor tissues confirmed antiangiogenic effect of Nos NPs. The findings highlighted efficacy of Nos NPs alone and in combination with Dox HCl on breast cancer tumors.
本研究旨在阐明载有依托泊苷（Nos）的聚合物纳米载体与多柔比星（Dox）联合应用对乳腺癌细胞的抗癌作用。采用纳米沉淀法制备载有 Nos 的甲氧基聚乙二醇（mPEG）、聚乳酸-羟基乙酸共聚物（PLGA）纳米颗粒（NPs）。采用透射电子显微镜（TEM）和动态光散射（DLS）对制备的 Nos NPs 进行表征。单独使用 Nos NPs 以及与 Dox 联合使用对 4T1 乳腺癌细胞系和小鼠模型进行抗癌活性评估。制备了球形 Nos NPs，其粒径为 101 ± 4.80nm，zeta 电位为-15.40 ± 1mV。傅里叶变换红外（FTIR）光谱结果表明，Nos 化学结构在制备过程中保持稳定。然而，差示扫描量热（DSC）热图谱证明，Nos NPs 中 Nos 的晶体状态变为无定形状态。Nos NPs 的包封效率%（EE%）和载药量%（DL%）分别约为 87.20 ± 3.50%和 12.50 ± 2.30%。游离态（盐酸依托泊苷，Nos HCl）和 Nos NPs 与盐酸多柔比星（Dox HCl）联合应用对 4T1 细胞均表现出协同抗癌作用。与 Nos NPs 和 Dox HCl 单独相比，Nos NPs 与 Dox HCl 的联合使用更有效地抑制了小鼠肿瘤的生长（68.50%）。肿瘤组织免疫组织化学（IHC）分析证实了 Nos NPs 的抗血管生成作用。这些发现突出了 Nos NPs 单独以及与 Dox HCl 联合应用对乳腺癌肿瘤的疗效。
