Department of Chemistry , Louisiana State University , Baton Rouge , Louisiana 70803 , United States.
Department of Comparative Biomedical Sciences, School of Veterinary Medicine , Louisiana State University , Baton Rouge , Louisiana 70803 , United States.
Mol Pharm. 2018 Sep 4;15(9):3837-3845. doi: 10.1021/acs.molpharmaceut.8b00339. Epub 2018 Jul 27.
Herein, we report on the role of endocytosis in the selective chemotherpeutic toxicity of rhodamine 6G (R6G) based nanomaterials, i.e., nanoGUMBOS, that are derived from a group of uniform materials based on organic salts (GUMBOS). Evaluation of cellular uptake in the presence and absence of endocytosis inhibitors suggests nanoGUMBOS internalization via clathrin-mediated endocytosis in cancer cells and reveals lack of endocytic internalization in normal cells. Results from characterization of these nanomaterials suggest that endocytic internalization in cancer cells leads to nanoGUMBOS dissociation within the endosomal environment. This ultimately results in selective cytotoxicity of the nanoGUMBOS for cancer cells with no toxicity toward normal cells under examined conditions. Following examination of the selectivity mechanism, in vivo investigations were performed to examine potential therapeutic properties of these nanoparticles. Remarkably, nanoGUMBOS treatment using a mouse xenograft model reduced the tumor volume by 50% suggesting retention of in vitro therapeutic properties in vivo. These results corroborate the selective behavior of nanoGUMBOS and demonstrate their in vivo therapeutic effects, providing further insight into the possible use of these nanomaterials as potential chemotherapeutic agents.
在这里，我们报告了内吞作用在基于罗丹明 6G（R6G）的纳米材料（即 nanoGUMBOS）的选择性化学毒性中的作用，这些纳米材料源自一组基于有机盐的均匀材料（GUMBOS）。在存在和不存在内吞作用抑制剂的情况下评估细胞摄取表明，nanoGUMBOS 通过网格蛋白介导的内吞作用在癌细胞中内化，并揭示了正常细胞中缺乏内吞作用内化。对这些纳米材料的特性的研究结果表明，癌细胞中的内吞作用内化导致内体环境中 nanoGUMBOS 的解离。这最终导致 nanoGUMBOS 对癌细胞具有选择性细胞毒性，而在检查条件下对正常细胞没有毒性。在检查了选择性机制后，进行了体内研究以检查这些纳米粒子的潜在治疗特性。值得注意的是，使用小鼠异种移植模型进行的 nanoGUMBOS 治疗使肿瘤体积减少了 50%，这表明在体内保留了体外治疗特性。这些结果证实了 nanoGUMBOS 的选择性行为，并证明了它们的体内治疗效果，为这些纳米材料作为潜在化疗药物的可能用途提供了进一步的见解。
