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枸杞多糖-铂类化合物的组装及其抗肿瘤活性。

The assembly and antitumor activity of lycium barbarum polysaccharide-platinum-based conjugates.

机构信息

Institute of Environmental Toxicology and Environmental Ecology, Yancheng Teachers University, Yancheng City, Jiangsu Province 224051, People's Republic of China; Chemistry and Chemical Engineering, Nanjing University of Technology, Nanjing City, Jiangsu Province 210009, People's Republic of China.

Institute of Environmental Toxicology and Environmental Ecology, Yancheng Teachers University, Yancheng City, Jiangsu Province 224051, People's Republic of China.

出版信息

J Inorg Biochem. 2020 Apr;205:111001. doi: 10.1016/j.jinorgbio.2020.111001. Epub 2020 Jan 24.

Abstract

In this work, the new polysaccharide-platinum conjugates of 5-aminosalicylic acid modified lycium barbarum polysaccharide linking platinum compounds were designed in order to construct an anticancer metal drug delivery system. The multiple analysis methods were used to describe the chemical structure and physical properties of the polysaccharide-metal conjugates. The results showed that 5-aminosalicylic acid successfully acted as linker which was covalently bound between polysaccharide and platinum compound. The morphology and rheological properties of polysaccharide have been changed by the formation of conjugates, which exhibited certain inhibition specificity to A549 (human lung cancer cell line). The agarose gel electrophoresis and fluorescence microscopy results demonstrated that such conjugates promoted the unwinding of DNA and could significantly damage the nucleus of A549 cells. Cell cycle analyzing the Pt complex of conjugates could cause intracellular DNA damage and induced G2 phase arrest. So, polysaccharide-platinum conjugates might find a range of applications, for example in metal anticancer drug delivery.

摘要

在这项工作中,设计了 5-氨基水杨酸修饰的枸杞多糖连接铂化合物的新型多糖-铂缀合物,以构建抗癌金属药物传递系统。采用多种分析方法描述了多糖-金属缀合物的化学结构和物理性质。结果表明,5-氨基水杨酸成功地作为连接物,将多糖与铂化合物共价结合。缀合物的形成改变了多糖的形态和流变性质,对 A549(人肺癌细胞系)表现出一定的抑制特异性。琼脂糖凝胶电泳和荧光显微镜结果表明,这些缀合物能促进 DNA 的解旋,并能显著损伤 A549 细胞的核。细胞周期分析表明,缀合物的铂配合物可引起细胞内 DNA 损伤并诱导 G2 期阻滞。因此,多糖-铂缀合物可能有广泛的应用,例如在金属抗癌药物传递中。

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