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基于铂(II)配位马齿苋多糖的金属药物基聚合物用于抗癌研究。

Platinum (II)-coordinated Portulaca oleracea polysaccharides as metal-drug based polymers for anticancer study.

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.

Cardio-Thoracic Surgery, Yancheng First People's Hospital, Yancheng, 224006, People's Republic of China.

出版信息

Colloids Surf B Biointerfaces. 2021 May;201:111628. doi: 10.1016/j.colsurfb.2021.111628. Epub 2021 Feb 18.

Abstract

Novel polysaccharide-platinum conjugated polymers bearing alendronate on Portulaca oleracea polysaccharides (PPS) were designed and synthesized. Their chemical structures and properties were characterized by Fourier transform infrared spectroscopy (FT-IR), H NMR and P NMR spectroscopy, Thermogravimetric analysis (TGA), X-ray powder diffraction (XRD), UV-vis spectrophotometer (UV-vis) and other analysis methods. The results demonstrated that alendronate can be used as the linker of Portulaca oleracea polysaccharides and platinum compounds. Portulaca oleracea polysaccharides-alendronate (PPS-ALN) conjugates exhibited stronger antioxidant ability than PPS. The cytotoxicity assay to cancer cells was tested in vitro, and the Portulaca oleracea polysaccharides-alendronate-platinum (PPS-ALN-Pt) conjugates strongly inhibited the proliferation of cancer cells than PPS and PPS-ALN. The evaluation of complexes affinity toward supercoiled plasmid DNA, displayed a high DNA interaction. Interestingly, the platinum conjugates displayed immunological competence in HeLa cells by cellular immunofluorescence assay. Besides, the cellular platinum accumulation of PPS-ALN-Pt conjugates was higher than that of cisplatin in HeLa cells, implying that the polysaccharide-platinum conjugated polymers might have a synergistically therapeutic application in metal anticancer drug delivery.

摘要

新型多膦酸酯-铂共轭聚合物通过马齿苋多糖(PPS)接枝阿仑膦酸钠(ALN)设计并合成。通过傅里叶变换红外光谱(FT-IR)、氢核磁(1H NMR)和磷核磁(31P NMR)光谱、热重分析(TGA)、X 射线粉末衍射(XRD)、紫外可见分光光度计(UV-vis)等分析方法对其化学结构和性质进行了表征。结果表明,阿仑膦酸钠可以作为马齿苋多糖和铂化合物的连接物。马齿苋多糖-阿仑膦酸钠(PPS-ALN)缀合物的抗氧化能力强于 PPS。体外细胞毒性试验表明,马齿苋多糖-阿仑膦酸钠-铂(PPS-ALN-Pt)缀合物比 PPS 和 PPS-ALN 更能抑制癌细胞的增殖。对复合物与超螺旋质粒 DNA 的亲和力评估显示出与 DNA 的高相互作用。有趣的是,通过细胞免疫荧光试验,铂缀合物在 HeLa 细胞中显示出免疫原性。此外,PPS-ALN-Pt 缀合物在 HeLa 细胞中的细胞内铂积累量高于顺铂,这表明多糖-铂共轭聚合物在金属抗癌药物递送中可能具有协同治疗应用。

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