Preparation and anti-triple-negative breast cancer cell effect of a nanoparticle for the codelivery of paclitaxel and gemcitabine

IF 4.703 3区 材料科学
Fan Yang, Zehui Fan, Lixia Zhang, Yanjuan He, Run Hu, Jinkun Xiang, Shiyang Fu, Guowei Wang, Jianlong Wang, Xiaojun Tao, Pan Zhang
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Abstract

Amphiphilic polymers (HA-ANI) were prepared by grafting hyaluronic acid (HA) and 6-(2-nitroimidazole)hexylamine (ANI) and then self-assemble in water to form nanoparticles (NPs) that could be loaded with paclitaxel (PTX) and gemcitabine (GEM) by dialysis. Infrared spectroscopy and 1H-NMR indicated the successful synthesis of HA-ANI. Three different ratios of NPs were prepared by adjusting the ratios of hydrophilic and hydrophobic materials, and the particle size decreased as the ratio of hydrophilic materials increased. When HA:ANI = 2.0:1, the nanoparticles had the smallest size distribution, good stability and near spherical shape and had high drug loading and encapsulation rates. In vitro release experiments revealed that NADPH could accelerate the drug release from NPs. Cellular uptake rate reached 86.50% at 6 h. The toxic effect of dual drug-loaded nanoparticles (P/G NPs) on MDA-MB-231 cells at 48 h was stronger than that of the free drug. The AO/EB double-staining assay revealed that a large number of late apoptotic cells appeared in the P/G NPs group, and the degree of cell damage was significantly stronger than that of the free drug group. In the cell migration assay, the 24 h-cell migration rate of the P/G NPs group was 5.99%, which was much lower than that of the free group (13.87% and 17.00%). In conclusion, MDA-MB-231 cells could effectively take up P/G NPs, while the introduction of the nano-codelivery system could significantly enhance the toxicity of the drug to MDA-MB-231 cells as well as the migration inhibition effect.

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紫杉醇和吉西他滨共给药纳米颗粒的制备和抗癌症三阴性细胞效应。
通过接枝透明质酸(HA)和6-(2-硝基咪唑)己胺(ANI),然后在水中自组装形成可通过透析负载紫杉醇(PTX)和吉西他滨(GEM)的纳米颗粒(NP),制备了两亲性聚合物(HA-ANI)。红外光谱和1H-NMR表明HA-ANI的合成是成功的。通过调节亲水性和疏水性材料的比例,制备了三种不同比例的纳米颗粒,并且随着亲水性材料比例的增加,颗粒尺寸减小。当HA:ANI = 2.0:1,纳米颗粒具有最小的尺寸分布、良好的稳定性和接近球形的形状,并且具有高的载药量和包封率。体外释放实验表明NADPH能加速药物从纳米颗粒中的释放。细胞摄取率在6h达到86.50%。双载药纳米颗粒(P/G NPs)在48小时对MDA-MB-231细胞的毒性作用强于游离药物。AO/EB双染色分析显示,P/G NPs组出现大量晚期凋亡细胞,细胞损伤程度明显强于游离药物组。在细胞迁移试验中,P/G NPs组的24小时细胞迁移率为5.99%,远低于游离组(13.87%和17.00%)。总之,MDA-MB-231细胞可以有效地吸收P/G NP,而纳米共给药系统的引入可以显著增强药物对MDA-MB/231细胞的毒性和迁移抑制作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Nanoscale Research Letters
Nanoscale Research Letters NANOSCIENCE & NANOTECHNOLOGY-MATERIALS SCIENCE, MULTIDISCIPLINARY
CiteScore
15.00
自引率
0.00%
发文量
110
审稿时长
2.5 months
期刊介绍: Nanoscale Research Letters (NRL) provides an interdisciplinary forum for communication of scientific and technological advances in the creation and use of objects at the nanometer scale. NRL is the first nanotechnology journal from a major publisher to be published with Open Access.
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