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靶向线粒体的纳米姜黄素可减轻 PKM2 和 FASN 的作用。

Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN.

机构信息

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China.

School of Chemistry and Chemical Engineering, Jiangsu University, Zhenjiang, 212013, PR China.

出版信息

Colloids Surf B Biointerfaces. 2019 Oct 1;182:110405. doi: 10.1016/j.colsurfb.2019.110405. Epub 2019 Jul 29.

Abstract

Tumor cells are sensitive to the disturbance of mitochondrial functions. Attenuation of dysfunctional mitochondria by natural compounds is an emerging strategy for the recovery of abnormal energy metabolism of cancer. To develop a nano-sized curcumin (CUR) in attenuating the energy metabolism of cancer cells, herein, a coral-shaped nano-transporter DNA-FeS-DA nanoparticle was synthesized using double-stranded DNA rich in 'GAG' and 'GC' series as a template and poly-dopamine as an adhesive. CUR was successfully loaded to DNA-FeS-DA with a molar ratio of ssDNA: CUR of 1:16, forming CUR@DNA-FeS-DA. This nano-curcumin can readily enter mitochondrion in MCF-7 cancer cells. The CUR@DNA-FeS-DA nanocomposite displays desirable photothermal effect and stability, while its CUR can be released gradually in the weak acid environment. The expression of both pyruvate kinase M2 and fatty acid synthase in the MCF-7 cancer cells were noticeably inhibited by CUR@DNA-FeS-DA. Given the controlled release and mitochondria-targeting properties, this CUR@DNA-FeS-DA nanocomposite is a promising new drug entity for intervening the energy metabolism of cancer cells.

摘要

肿瘤细胞对线粒体功能的紊乱敏感。天然化合物对功能失调的线粒体的衰减是恢复癌细胞异常能量代谢的一种新兴策略。为了开发纳米级姜黄素(CUR)以减轻癌细胞的能量代谢,本文使用富含“GAG”和“GC”系列的双链 DNA 作为模板和聚多巴胺作为黏附剂合成了珊瑚状纳米转运体 DNA-FeS-DA 纳米颗粒。CUR 成功地以 ssDNA:CUR 的摩尔比为 1:16 加载到 DNA-FeS-DA 上,形成 CUR@DNA-FeS-DA。这种纳米姜黄素可以很容易地进入 MCF-7 癌细胞的线粒体。CUR@DNA-FeS-DA 纳米复合材料表现出理想的光热效应和稳定性,同时其 CUR 可以在弱酸环境中逐渐释放。CUR@DNA-FeS-DA 明显抑制 MCF-7 癌细胞中丙酮酸激酶 M2 和脂肪酸合酶的表达。鉴于其控制释放和靶向线粒体的特性,这种 CUR@DNA-FeS-DA 纳米复合材料是干预癌细胞能量代谢的一种很有前途的新药物实体。

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