Comparison of Chemotherapeutic Activities of Rhodamine-Based GUMBOS and NanoGUMBOS
Comparison of Chemotherapeutic Activities of Rhodamine-Based GUMBOS and NanoGUMBOS
复制标题
DOI：
10.3390/molecules25143272
复制
发表时间：
2020-07-01
期刊：
影响因子：
4.6
通讯作者：
Warner, Isiah M.
中科院分区：
文献类型：
--
作者：
Bhattarai, Nimisha;Chen, Mi;Warner, Isiah M.
罗丹明类化合物因其亲脂性阳离子结构所致的线粒体靶向和化疗特性而被广泛研究。在以往的研究中，我们已经发现，罗丹明6G转化为纳米GUMBOS，即从一组基于有机盐的均匀材料(GUMBOS)衍生的纳米材料，导致对癌细胞的选择性化疗毒性高于正常细胞。在这里，我们研究了四种不同罗丹明衍生物的GUMBOS的化疗活性，其中两种含酯基，即罗丹明123(R123)和SNAFR-5，两种含羧酸基，即罗丹明110(R110)和罗丹明B(RB)。在这项研究中，我们评估(1)辛醇-水分配系数的相对疏水性，(2)细胞毒性，和(3)细胞摄取，以评估这些不同化合物之间可能的构效关系。有趣的是，我们发现虽然R123和SNAFR-5衍生的GUMBOS在水介质中形成了纳米GUMBOS，但Rb和R110 GUMBOS没有观察到明显的纳米颗粒。进一步的研究表明，R110和RB GUMBOS相对较高的水溶性阻碍了纳米粒子的形成。随后，虽然R123和SNAFR-5显示出与先前研究的R6G Nano GUMBOS相似的选择性化疗毒性，但R110和Rb GUMBOS缺乏这一特性。此外，R123和SNAFR-5纳米GUMBOS的化疗毒性也明显高于R110和Rb GUMBOS。与R123和SNAFR-5化合物相比，观察结果与细胞对R110和Rb的摄取减少一致。此外，这些结果也与先前的观察结果一致，即纳米颗粒的形成对观察到的选择性化疗特性以及罗丹明纳米GUMBOS的化疗效果至关重要。
Rhodamine derivatives have been widely investigated for their mitochondrial targeting and chemotherapeutic properties that result from their lipophilic cationic structures. In previous research, we have found that conversion of Rhodamine 6G into nanoGUMBOS, i.e., nanomaterials derived from a group of uniform materials based on organic salts (GUMBOS), led to selective chemotherapeutic toxicity for cancer cells over normal cells. Herein, we investigate the chemotherapeutic activity of GUMBOS derived from four different rhodamine derivatives, two bearing an ester group, i.e., Rhodamine 123 (R123) and SNAFR-5, and two bearing a carboxylic acid group, i.e., rhodamine 110 (R110) and rhodamine B (RB). In this study, we evaluate (1) relative hydrophobicity via octanol-water partition coefficients, (2) cytotoxicity, and (3) cellular uptake in order to evaluate possible structure-activity relationships between these different compounds. Intriguingly, we found that while GUMBOS derived from R123 and SNAFR-5 formed nanoGUMBOS in aqueous medium, no distinct nanoparticles are observed for RB and R110 GUMBOS. Further investigation revealed that the relatively high water solubility of R110 and RB GUMBOS hinders nanoparticle formation. Subsequently, while R123 and SNAFR-5 displayed selective chemotherapeutic toxicity similar to that of previously investigated R6G nanoGUMBOS, the R110 and RB GUMBOS were lacking in this property. Additionally, the chemotherapeutic toxicities of R123 and SNAFR-5 nanoGUMBOS were also significantly greater than R110 and RB GUMBOS. Observed results were consistent with decreased cellular uptake of R110 and RB as compared to R123 and SNAFR-5 compounds. Moreover, these results are also consistent with previous observations that suggest that nanoparticle formation is critical to the observed selective chemotherapeutic properties as well as the chemotherapeutic efficacy of rhodamine nanoGUMBOS.