Laboratory of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, 1 Weigang, Nanjing 210095, PR China.
State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, 2 Sipailou, Nanjing 210096, PR China.
Colloids Surf B Biointerfaces. 2015 Feb 1;126:198-203. doi: 10.1016/j.colsurfb.2014.12.023. Epub 2014 Dec 31.
Recently, increased reactive oxygen species (ROS) levels and altered redox status in cancer cells have become a novel therapeutic strategy to improve cancer selectivity over normal cells. It has been known that silver nanoparticles (AgNPs) display anti-leukemic activity via ROS overproduction. Hence, we hypothesized that AgNPs could improve therapeutic efficacy of ROS-generating agents against leukemia cells. In the current study, N-(4-hydroxyphenyl)retinamide (4-HPR), a synthetic retinoid, was used as a drug model of ROS induction to investigate its synergistic effect with AgNPs. The data exhibited that AgNPs with uniform size prepared by an electrochemical method could localize in the lysosomes, mitochondria and cytoplasm of SHI-1 cells. More importantly, AgNPs together with 4-HPR could exhibit more cytotoxicity and apoptosis via overproduction of ROS in comparison with that alone. Taken together, these results reveal that AgNPs combined with ROS-generating drugs could potentially enhance therapeutic efficacy against leukemia cells, thereby providing a novel strategy for AgNPs in leukemia therapy.
最近，癌细胞中活性氧（ROS）水平的增加和氧化还原状态的改变已成为一种新的治疗策略，以提高癌症对正常细胞的选择性。已知银纳米粒子（AgNPs）通过过度产生 ROS 显示出抗白血病活性。因此，我们假设 AgNPs 可以提高产生 ROS 的药物对白血病细胞的治疗效果。在本研究中，N-(4-羟基苯基)视黄酰胺（4-HPR），一种合成维甲酸，被用作 ROS 诱导的药物模型，以研究其与 AgNPs 的协同作用。结果表明，通过电化学方法制备的均匀尺寸的 AgNPs 可以定位于 SHI-1 细胞的溶酶体、线粒体和细胞质中。更重要的是，与单独使用相比，AgNPs 与 4-HPR 一起可以通过过度产生 ROS 表现出更高的细胞毒性和细胞凋亡。总之，这些结果表明，AgNPs 与产生 ROS 的药物联合使用可能会增强对白血病细胞的治疗效果，从而为 AgNPs 在白血病治疗中的应用提供了一种新策略。
