Fabrication of dopamine conjugated with protein @metal organic framework for targeted drug delivery: A biocompatible pH-Responsive nanocarrier for gemcitabine release on MCF-7 human breast cancer cells
Fabrication of dopamine conjugated with protein @metal organic framework for targeted drug delivery: A biocompatible pH-Responsive nanocarrier for gemcitabine release on MCF-7 human breast cancer cells
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DOI：
10.1016/j.bioorg.2021.105467
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发表时间：
2022-01-01
影响因子：
5.1
通讯作者：
Ozacar, Mahmut
中科院分区：
文献类型：
--
作者：
Abd Al-jabbar, Shatha;Atiroglu, Vesen;Ozacar, Mahmut
金属有机结构（MOF）是由金属离子和有机配位分子组成的一种高度增殖的现代材料，具有比表面积大、孔容宽、功能性强和上级载药性能好等特点，已成为一种很有前途的生物医用材料。本研究将抗癌药物盐酸吉西他滨（Gemcitabine Hydrochloride，Gem）和苦杏仁苷（Amygdalin，Amy）负载到以牛血清白蛋白（BSA）为中心、沸石咪唑骨架-8（ZIF-8）为pH敏感保护涂层的纳米复合材料结构中。将合成的BSA-Gem@ZIF-8和BSA-Gem-Amy@ZIF-8依次进行聚多巴胺包覆、Au 3+螯合和没食子酸（GA）偶联，最终得到ZIF-8结构的多功能纳米载体，并通过不同的表征方法证实了纳米载体的成功制备。由于ZIF-8的性质，在体外研究中观察到BSA-Gem@ZIF-8/Dopa/GA和BSA-Gem-Amy@ZIF-8/Dopa/GA的pH依赖性释放。使用WST-1和吖啶橙子染色在MCF-7人乳腺癌和HUVEC对照细胞系中评价这些纳米载体的细胞毒性和凋亡作用。体外细胞毒性研究表明，BSA-Gem@ZIF-8/Dopa/GA和BSA-Gem-Amy@ZIF-8/Dopa/GA在MCF-7细胞中比单独的吉西他滨更有效，在HUVEC细胞中毒性更小。此外，两种pH响应性纳米载体在MCF-7细胞中诱导更多的凋亡性细胞死亡。因此，我们认为，基于ZIF-8构建的多功能纳米载体可能是吉西他滨用于癌症治疗的替代治疗策略。
Metal-organic structures (MOF), modern extremely proliferous materials consisting of metal ions and organic coordinating molecules, has become a promising biomedical material because of its unusual features, including great surface area, wide pore volume, flexible functionality and superior performance for drug loading. In the current investigation, Gemcitabine Hydrochloride (Gem), an anticancer drug, and Amygdalin (Amy) were loaded into a nanocomposite structure formed from bovine serum albumin (BSA) as a center and zeolytic imidazolate framework-8 (ZIF-8) as a pH sensitive protective coating. The formed BSA-Gem@ZIF-8 and BSA-Gem-Amy@ZIF-8 were successively coated by polydopamine, chelated by Au3+ and conjugated via gallic acid (GA), acquired ZIF-8 structure as a multifunctional nanocarrier at the end.It was confirmed by different characterization methods that the nanocarrier was successfully produced. Due to the nature of ZIF-8, pH dependent releases of BSA-Gem@ZIF-8/Dopa/GA and BSA-Gem-Amy@ZIF-8/Dopa/GA were observed in in vitro studies. Cytotoxicity and apoptotic effects of these nanocarriers were evaluated using WST-1 and acridine orange staining in MCF-7 human breast cancer and HUVEC control cell lines. In-vitro cytotoxicity studies showed that both BSA-Gem@ZIF-8/Dopa/GA and BSA-Gem-Amy@ZIF-8/Dopa/GA were more effective than gemcitabine alone in MCF-7 cells with less toxicity in HUVEC cells. Additionally, both pH-responsive nanocarriers induced more apoptotic cell death in MCF-7 cells. We therefore believe that the built multifunctional nanocarrier based on ZIF-8 could be an alternative therapeutic strategy the use of gemcitabine for cancer therapy.