制备多巴胺与蛋白质@金属有机框架的复合物用于靶向药物递送:一种用于 MCF-7 人乳腺癌细胞中海拉滨释放的生物相容性 pH 响应性纳米载体。
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.
机构信息
Karbala University, Faculty of Medicine, Department of Biochemistry, 54187 Karbala, Iraq.
Sakarya University, Biomaterials, Energy, Photocatalysis, Enzyme Technology, Nano & Advanced Materials, Additive Manufacturing, Environmental Applications and Sustainability Research & Development Group (BIOENAMS R & D Group), 54187 Sakarya, Turkey; Sakarya University, Biomedical, Magnetic and Semiconductor Materials Application and Research Center (BIMAS-RC), 54187 Sakarya, Turkey.
出版信息
Bioorg Chem. 2022 Jan;118:105467. doi: 10.1016/j.bioorg.2021.105467. Epub 2021 Nov 10.
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 Au 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.
金属有机骨架(MOF)是一种由金属离子和有机配位分子组成的新型、极富生命力的材料,由于其具有独特的特性,如大比表面积、大孔体积、灵活的功能以及出色的载药性能,已成为一种有前途的生物医学材料。在本研究中,盐酸吉西他滨(Gem)作为一种抗癌药物,和苦杏仁苷(Amy)被载入由牛血清白蛋白(BSA)作为中心和沸石咪唑酯骨架-8(ZIF-8)作为 pH 敏感保护层形成的纳米复合材料结构中。所形成的 BSA-Gem@ZIF-8 和 BSA-Gem-Amy@ZIF-8 被聚多巴胺连续包覆,通过 Au 螯合,并通过没食子酸(GA)进行连接,最终获得 ZIF-8 结构的多功能纳米载体。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了 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 和吖啶橙染色在 MCF-7 人乳腺癌和 HUVEC 对照细胞系中评估了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 细胞中的效果均优于单独使用吉西他滨,且在 HUVEC 细胞中的毒性更小。此外,两种 pH 响应性纳米载体在 MCF-7 细胞中诱导了更多的凋亡性细胞死亡。因此,我们认为基于 ZIF-8 的构建多功能纳米载体可以作为替代的治疗策略,用于癌症治疗中的吉西他滨的使用。