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多分支离子液体-壳聚糖作为一种智能且生物相容的纳米载体,具有隐形和靶向特性,用于联合化疗。

Multi-branched ionic liquid-chitosan as a smart and biocompatible nano-vehicle for combination chemotherapy with stealth and targeted properties.

机构信息

Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz 5166614766, Iran.

Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran; Drug Applied Research Centre, School of Advanced Medical Science, and Department of Medical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Carbohydr Polym. 2018 Sep 15;196:299-312. doi: 10.1016/j.carbpol.2018.05.059. Epub 2018 May 18.


DOI:10.1016/j.carbpol.2018.05.059
PMID:29891300
Abstract

A possible approach for clinical cancer treatment is combination chemotherapy. To address this issue, many anticancer agents have been used simultaneously to achieve synergistic effects with the different mechanism of actions, however, their toxic side effects are still a big challenge. In this study, a smart, biocompatible, magnetic nanocarrier composed of multi-branched ionic liquid-chitosan grafted mPEG was designed and used for targeted multidrug delivery of DOX and MTX as model anticancer agents to MCF7 breast cancer cells. The results of hemolysis assay on human red blood cells and cytotoxicity studies indicated that blank nanocarrier has no significant hemolytic and cytotoxic effects in MCF7 cells as observed in the results of MTT assay, however, drugs-loaded nanocarrier could decrease the viability of MCF7 cells in a dose-dependent manner. To further simulate the interaction of nanocarrier with plasma proteins, the SDS-PAGE assay was performed after the nanocarrier was incubated with human plasma and the results indicated that a series of proteins were attached to the surface of nanocarrier leading protein-particle corona complex. This complex gives a stealth property as well as increasing cellular uptake process due to the presence of proteins acting as ligands for receptors in the surface of cancer cells that are suitable for drug delivery systems. The efficiency of dual-drug delivery was also confirmed by cellular uptake and DAPI staining. All these results persuade us, this nanocarrier is suitable for use in further animal studies in future investigations.

摘要

癌症临床治疗的一种可能方法是联合化疗。为了解决这个问题,许多抗癌药物已经被同时使用,以实现协同作用,具有不同的作用机制,然而,它们的毒性副作用仍然是一个巨大的挑战。在这项研究中,设计了一种智能的、生物相容的、由多分支离子液体-壳聚糖接枝 mPEG 组成的磁性纳米载体,用于 DOX 和 MTX 作为模型抗癌药物的靶向多药递送,以 MCF7 乳腺癌细胞。人红细胞溶血试验和细胞毒性研究结果表明,空白纳米载体在 MCF7 细胞中没有明显的溶血和细胞毒性作用,如 MTT 试验结果所示,然而,载药纳米载体可以以剂量依赖的方式降低 MCF7 细胞的活力。为了进一步模拟纳米载体与血浆蛋白的相互作用,在纳米载体与人血浆孵育后进行 SDS-PAGE 分析,结果表明一系列蛋白质附着在纳米载体表面,形成蛋白-颗粒冠状复合物。由于存在作为癌细胞表面受体配体的蛋白质,这种复合物具有隐身特性,并增加细胞摄取过程,适合作为药物递送系统。通过细胞摄取和 DAPI 染色也证实了双重药物递送的效率。所有这些结果都使我们相信,这种纳米载体适合在未来的研究中进一步进行动物研究。

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[4]
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[10]
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