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用于顺铂持续递送的纳米结构化功能化磁性平台:合成、表征和体外细胞毒性评价。

Nanostructured functionalized magnetic platforms for the sustained delivery of cisplatin: Synthesis, characterization and in vitro cytotoxicity evaluation.

机构信息

Departamento de Química, Universidade de Aveiro, 3810-193 Aveiro, Portugal; CICECO-Instituto de Materiais de Aveiro, Universidade de Aveiro, Portugal.

Unidade de Bioquímica, Departamento de Biomedicina, Faculdade de Medicina do Porto, Universidade do Porto, Portugal; I3S, Universidade do Porto, Portugal.

出版信息

J Inorg Biochem. 2020 Dec;213:111258. doi: 10.1016/j.jinorgbio.2020.111258. Epub 2020 Oct 3.

Abstract

Cisplatin has demonstrated extraordinary anticancer activity against a variety of solid tumors. However, its clinical efficacy is contrasted by its toxicity profile. Having in mind the need to reduce the toxicity, promote a sustained release and enhance the body-circulation time of cisplatin, herein novel nanocarriers consisting of core-shell silica-coated iron oxide nanoparticles functionalized with dicarboxylic acid groups were prepared and characterized. Cisplatin was conjugated with the functionalized nanoparticles by surface tethering. Controlled release of cisplatin was observed without burst effect and in a sustained profile for up to 3 days. In vitro studies showed cytotoxic and antiproliferative effects of the cisplatin nanoconjugates against a human pancreatic cancer cell line. Importantly, when compared with free cisplatin, nanoconjugates exhibited lower cytotoxic effects regarding nonmalignant human duct pancreatic cells.

摘要

顺铂对多种实体瘤表现出非凡的抗癌活性。然而,其临床疗效与毒性特征形成鲜明对比。为了降低顺铂的毒性,促进其持续释放并延长其在体内的循环时间,本研究制备并表征了由核壳结构的二氧化硅包裹的氧化铁纳米粒子组成的新型纳米载体,这些纳米粒子通过二羧酸基团进行了功能化修饰。顺铂通过表面连接键合到功能化纳米粒子上。观察到顺铂的释放没有突释效应,并呈现持续释放达 3 天。体外研究表明,顺铂纳米复合物对人胰腺癌细胞系具有细胞毒性和抗增殖作用。重要的是,与游离顺铂相比,纳米复合物对非恶性人胆管胰腺细胞的细胞毒性作用较低。

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