Synthesis and evaluation of the cytotoxic and anti-proliferative properties of ZnO quantum dots against MCF-7 and MDA-MB-231 human breast cancer cells.
Synthesis and evaluation of the cytotoxic and anti-proliferative properties of ZnO quantum dots against MCF-7 and MDA-MB-231 human breast cancer cells.
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DOI：
10.1016/j.msec.2017.08.014
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发表时间：
2017-12
期刊：
影响因子：
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通讯作者：
R. A;Srikanth Jagadeesan;Y. Cho;J. Lim;K. Choi
中科院分区：
文献类型：
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作者：
R. A;Srikanth Jagadeesan;Y. Cho;J. Lim;K. Choi
目前治疗研究的趋势是将纳米材料载体应用于癌症治疗。其中一个这样的分子，ZnO，最初用于诊断和作为药物载体，因其生物学特性而变得越来越重要。在这里，我们首次报告了ZnO量子点对MCF-7和转移性MDA-MB-231人乳腺癌细胞的增强细胞毒性的范围。与其他ZnO纳米结构不同，ZnO QD分散且尺寸小（8-10 nm），这被认为大大增加了细胞摄取。此外，酸性肿瘤微环境吸引ZnO QDs增强靶向治疗，同时使正常细胞受影响较小。MTT法结果表明，与其他报道的ZnO纳米结构相比，ZnO量子点在很低的浓度（10和15 μg/ml）下就能诱导MCF-7和转移性MDA-MB-231乳腺癌细胞的细胞毒性。HEK-293细胞在这些浓度下显示出较低的毒性。DAPI染色和TUNEL检测的共聚焦显微镜图像表明，ZnO量子点诱导MCF-7和MDA-MB-231的核碎裂和凋亡。流式细胞仪结果表明，ZnO量子点处理诱导细胞周期停滞在G 0/G1期在这些细胞。ZnO量子点显著降低MCF-7和MDA-MB-231的增殖和迁移，分别从克隆形成和伤口愈合测定的结果中看出。此外，我们的数据表明，ZnO量子点通过Bax和Bcl-2蛋白调节细胞凋亡，通过免疫荧光和Western blot验证。总之，我们的研究结果表明，这些超小尺寸的ZnO量子点通过利用其酸性肿瘤微环境使癌细胞不稳定，从而诱导细胞凋亡并在低剂量下控制细胞增殖和迁移。
Current trends in therapeutic research are the application of nanomaterial carriers for cancer therapy. One such molecule, ZnO, originally used in diagnosis and as a drug carrier, is gaining importance for its biological properties. Here, we report for the first time, the scope of ZnO QDs for enhanced cytotoxicity against MCF-7 and metastatic MDA-MB-231 human breast cancer cells. Unlike other ZnO nanostructures, ZnO QDs are dispersed and small sized (8–10 nm) which is believed to greatly increase the cellular uptake. Furthermore, the acidic tumor microenvironment attracts ZnO QDs enhancing targeted therapy while leaving normal cells less affected. Results from MTT assay demonstrated that ZnO QDs induced cytotoxicity to MCF-7 and metastatic MDA-MB-231 breast cancer cells at very low concentrations (10 and 15 μg/ml) as compared to other reported ZnO nanostructures. HEK-293 cells showed less toxicity at these concentrations. Confocal microscope images from DAPI staining and TUNEL assay demonstrated that ZnO QDs induced nuclear fragmentation and apoptosis in MCF-7 and MDA-MB-231. FACS results suggested ZnO QDs treatment induced cell cycle arrest at the G0/G1 phase in these cells. ZnO QDs drastically decreased the proliferation and migration of MCF-7 and MDA-MB-231 as seen from the results of the clonogenic and wound healing assays respectively. Furthermore, our data suggested that ZnO QDs regulated apoptosis via Bax and Bcl-2 proteins as validated by immunofluorescence and western blot. Taken together, our findings demonstrate that these ultra-small sized ZnO QDs destabilize cancer cells by using its acidic tumor microenvironment thereby inducing apoptosis and controlling the cell proliferation and migration at low dosages.