Chen Mi, Bhattarai Nimisha, Cong Mingyan, Pérez Rocío L, McDonough Karen C, Warner Isiah M
Department of Chemistry, Louisiana State University Baton Rouge LA 70803 USA
AgCenter Biotechnology Labs, Louisiana State University Baton Rouge LA 70803 USA.
RSC Adv. 2018 Sep 12;8(55):31700-31709. doi: 10.1039/c8ra05484c. eCollection 2018 Sep 5.
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, 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.
在此，我们提出并展示了一种简单的抗衡离子变化策略，用于设计一系列基于近红外IR780的纳米GUMBOS（基于有机盐的一组均匀材料的纳米材料），以产生增强的抗癌活性。这些纳米材料是通过使用再沉淀法对基于IR780的GUMBOS进行直接纳米工程合成的，无需添加任何其他材料。因此，这些新型纳米材料可作为无载体纳米药物，与传统化疗药物相比具有几个明显的优势。对这些纳米GUMBOS的尺寸和稳定性的研究表明，形成了在生物条件下稳定的约100纳米纳米颗粒。有趣的是，这些纳米GUMBOS的化疗应用表明，与母体染料相比，对乳腺癌细胞的毒性增强了两到四倍，同时对正常细胞仍保持最小毒性。还通过研究它们的亚细胞定位以及使用线粒体毒性测定法来研究这些纳米GUMBOS的癌症毒性机制。对这些研究数据的分析表明，所有纳米GUMBOS主要积聚在癌细胞的线粒体中，并使线粒体功能失调以诱导细胞死亡。通过这些研究，我们证明了通过简单改变抗衡离子，基于IR780的纳米GUMBOS具有可调节的特性，从而为未来设计用于癌症治疗的更好的纳米药物提供了一种有前景的策略。
