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曲妥珠单抗-树枝状大分子-氟化物药物递送系统在乳腺癌体外治疗中的分析研究。

An analytical study of Trastuzumab-dendrimer-fluorine drug delivery system in breast cancer therapy in vitro.

机构信息

Department of Biochemistry and General Chemistry, Medical College of University of Rzeszów, Rzeszów, Poland.

Department of Biotechnology, Natural Sciences College of University of Rzeszów, Rzeszów, Poland.

出版信息

Biomed Pharmacother. 2021 Jan;133:111053. doi: 10.1016/j.biopha.2020.111053. Epub 2020 Dec 1.

Abstract

UNLABELLED

Trastuzumab is considered to be a fundamental drug for treatment of breast cancer with Her-2 overexpression (Her-2 positive cells). Trastuzumab is a monoclonal antibody that targets the Her-2 receptor. Trastuzumab treatment used in breast cancer therapy require a visualization to validate their delivery and response. The objective of this study was to investigate Trastuzumab-dendrimer-fluorine drug delivery system by synthesis and characterization of a series of fluorinated dendrimers.

MATERIALS AND METHODS

Trastuzumab-dendrimer-fluorine drug delivery system is a covalent attachment of Trastuzumab to fluorinated dendrimers. We design synthesis and evaluate main product by using electrophoresis, HPLC and LC-MS techniques. We prepared three-dimensional breast cancer cell culture in bioreactor device. For the cell culture we used MCF-7 cells with Her-2 overexpression to study Trastuzumab-dendrimer-fluorine drug delivery system efficacy. We evaluate efficacy by Magnetic Resonance Imaging (MRI) relaxation time.

RESULTS

An analytical analysis showed that synthesis of Trastuzumab-dendrimer-fluorine drug delivery system is possible to obtain with a good yield. The results obtained indicated potential of Trastuzumab-dendrimer-fluorine drug delivery system is more efficient than trastuzumab alone. Chromatographic and electrophoretic separations showed that the synthetized conjugates were a Trastuzumab-dendrimer-fluorine drug delivery systems. The hight synthesis efficiency was found. The presence of molecules with lower masses than trastuzumab can have influence on efficiency.

CONCLUSIONS

Trastuzumab-dendrimer-fluorine drug delivery system is a new form of Trastuzumab to treat breast cancer cells in vitro. Due to presence of F nuclei the system can be monitored by MRI measurements.

摘要

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曲妥珠单抗被认为是治疗 Her-2 过表达(Her-2 阳性细胞)乳腺癌的基本药物。曲妥珠单抗是一种针对 Her-2 受体的单克隆抗体。曲妥珠单抗治疗乳腺癌需要通过可视化来验证其输送和反应。本研究的目的是通过合成和表征一系列氟代树突聚合物来研究曲妥珠单抗-树突聚合物-氟化物药物传递系统。

材料和方法

曲妥珠单抗-树突聚合物-氟化物药物传递系统是通过将曲妥珠单抗共价连接到氟代树突聚合物上形成的。我们通过电泳、HPLC 和 LC-MS 技术设计、合成和评估主要产物。我们在生物反应器装置中制备三维乳腺癌细胞培养物。我们使用 Her-2 过表达的 MCF-7 细胞进行细胞培养,以研究曲妥珠单抗-树突聚合物-氟化物药物传递系统的疗效。我们通过磁共振成像(MRI)弛豫时间来评估疗效。

结果

分析表明,曲妥珠单抗-树突聚合物-氟化物药物传递系统的合成可以获得良好的产率。得到的结果表明,曲妥珠单抗-树突聚合物-氟化物药物传递系统的潜力比单独使用曲妥珠单抗更有效。色谱和电泳分离表明,合成的缀合物是曲妥珠单抗-树突聚合物-氟化物药物传递系统。发现合成效率较高。分子量低于曲妥珠单抗的分子的存在可能会影响效率。

结论

曲妥珠单抗-树突聚合物-氟化物药物传递系统是治疗乳腺癌细胞的一种新形式的曲妥珠单抗。由于存在 F 核,该系统可以通过 MRI 测量进行监测。

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