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Mitochondria targeting IR780-based nanoGUMBOS for enhanced selective toxicity towards cancer cells

机译：线粒体靶向基于IR780的纳米镜，用于增强对癌细胞的选择性毒性

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摘要

Herein, a simple counter-ion variation strategy is proposed and demonstrated for design of an array of near infrared IR780-based nanoGUMBOS (nanomaterials from a Group of Uniform Materials Based on Organic Salts) to produce enhanced anticancer activity. These nanomaterials were synthesized by direct nanoengineering of IR780-based GUMBOS using a reprecipitation method, without addition of any other materials. Thus, these novel nanomaterials can serve as carrier-free nanodrugs, providing several distinct advantages over conventional chemotherapeutics. Examination of the size and stability of these nanoGUMBOS indicates formation of approximately 100 nm nanoparticles that are stable under biological conditions. Interestingly, in vitro chemotherapeutic applications of these nanoGUMBOS indicate two to four-fold enhanced toxicity towards breast cancer cells as compared to the parent dye, while still maintaining minimal toxicity towards normal cells. The mechanism of cancer toxicity for these nanoGUMBOS was also examined by a study of their sub-cellular localization as well as using a mitochondrial toxicity assay. Analyses of data from these studies revealed that all nanoGUMBOS primarily accumulate in the mitochondria of cancer cells and produce dysfunction in the mitochondria to induce cell death. Using these studies, we demonstrate tunable properties of IR780-based nanoGUMBOS through simple variation of counter-ions, thus providing a promising strategy for future design of better nanomedicines to be used for cancer therapy.
机译：在本文中，一个简单的反离子变异策略提出并证明了（从统一材料组基于有机盐的纳米材料）近红外基于IR780-nanoGUMBOS的阵列的设计，以产生增强的抗癌活性。这些纳米材料通过使用再沉淀法基于IR780-GUMBOS的直接纳米设计合成，不添加任何其它材料制成。因此，这些纳米材料新颖可以作为无载体nanodrugs，用常规化疗药物提供几个明显的优势。这些nanoGUMBOS的尺寸和稳定性的检查表明形成了约100nm的纳米颗粒在生物条件下是稳定的。有趣的是，在体外这些nanoGUMBOS的化疗应用指示两个到四倍相比于亲染料，同时仍然保持对正常细胞的毒性最小朝向乳腺癌细胞毒性增强。也可以通过亚细胞定位的研究，以及使用线粒体毒性法检测癌症毒性这些nanoGUMBOS的机制。从这些研究数据的分析显示，所有nanoGUMBOS在癌细胞中线粒体产生功能障碍的线粒体主要积累诱导细胞死亡。通过这些研究，我们展示了通过抗衡离子的简单变化基于IR780-nanoGUMBOS的可调性，从而提供更好的纳米医学的未来设计一个有前途的策略，用于癌症治疗。

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  • 来源
    《RSC Advances》 |2018年第55期|共10页
  • 作者

    Chen Mi; Bhattarai Nimisha; Cong Mingyan; Perez Rocio L.; McDonough Karen C.; Warner Isiah M.;

  • 作者单位

    Louisiana State Univ Dept Chem Baton Rouge LA 70803 USA;

    Louisiana State Univ Dept Chem Baton Rouge LA 70803 USA;

    Louisiana State Univ Dept Chem Baton Rouge LA 70803 USA;

    Louisiana State Univ Dept Chem Baton Rouge LA 70803 USA;

    Louisiana State Univ AgCtr Biotechnol Labs Baton Rouge LA 70803 USA;

    Louisiana State Univ Dept Chem Baton Rouge LA 70803 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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