Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Korea.
Int J Mol Sci. 2018 Mar 1;19(3):710. doi: 10.3390/ijms19030710.
The use of graphene to target and eliminate cancer stem cells (CSCs) is an alternative approach to conventional chemotherapy. We show the biomolecule-mediated synthesis of reduced graphene oxide-silver nanoparticle nanocomposites (rGO-Ag) using R-phycoerythrin (RPE); the resulting RPE-rGO-Ag was evaluated in human ovarian cancer cells and ovarian cancer stem cells (OvCSCs). The synthesized RPE-rGO-Ag nanocomposite (referred to as rGO-Ag) was characterized using various analytical techniques. rGO-Ag showed significant toxicity towards both ovarian cancer cells and OvCSCs. After 3 weeks of incubating OvCSCs with rGO-Ag, the number of A2780 and ALDH⁺CD133⁺ colonies was significantly reduced. rGO-Ag was toxic to OvCSCs and reduced cell viability by mediating the generation of reactive oxygen species, leakage of lactate dehydrogenase, reduced mitochondrial membrane potential, and enhanced expression of apoptotic genes, leading to mitochondrial dysfunction and possibly triggering apoptosis. rGO-Ag showed significant cytotoxic potential towards highly tumorigenic ALDH⁺CD133⁺ cells. The combination of rGO-Ag and salinomycin induced 5-fold higher levels of apoptosis than each treatment alone. A combination of rGO-Ag and salinomycin at very low concentrations may be suitable for selectively killing OvCSCs and sensitizing tumor cells. rGO-Ag may be a novel nano-therapeutic molecule for specific targeting of highly tumorigenic ALDH⁺CD133⁺ cells and eliminating CSCs. This study highlights the potential for targeted therapy of tumor-initiating cells.
利用石墨烯靶向和消除癌症干细胞（CSCs）是一种替代传统化疗的方法。我们展示了使用藻红蛋白（RPE）介导的还原氧化石墨烯-银纳米粒子纳米复合材料（rGO-Ag）的生物分子合成；所得到的 RPE-rGO-Ag 在人卵巢癌细胞和卵巢癌症干细胞（OvCSCs）中进行了评估。使用各种分析技术对合成的 RPE-rGO-Ag 纳米复合材料（简称 rGO-Ag）进行了表征。rGO-Ag 对卵巢癌细胞和 OvCSCs 均表现出显著的毒性。在用 rGO-Ag 孵育 OvCSCs 3 周后，A2780 和 ALDH⁺CD133⁺集落的数量明显减少。rGO-Ag 通过介导活性氧的产生、乳酸脱氢酶的泄漏、线粒体膜电位的降低以及凋亡基因的表达增强来介导细胞毒性，从而导致线粒体功能障碍和可能触发细胞凋亡，从而降低 OvCSCs 的细胞活力。rGO-Ag 对高度致瘤性的 ALDH⁺CD133⁺细胞具有显著的细胞毒性潜力。rGO-Ag 和沙利霉素的组合诱导的凋亡水平比每种药物单独处理时高 5 倍。非常低浓度的 rGO-Ag 和沙利霉素的组合可能适合于选择性杀伤 OvCSCs 和增敏肿瘤细胞。rGO-Ag 可能是一种新型的纳米治疗分子，可用于特异性靶向高度致瘤性的 ALDH⁺CD133⁺细胞并消除 CSCs。本研究强调了针对肿瘤起始细胞的靶向治疗的潜力。
