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ZnO nanoparticles stimulate oxidative stress to induce apoptosis of B16F10 melanoma cells: In vitro and in vivo studies
Biomedical Physics & Engineering Express ( IF 1.3 ) Pub Date : 2021-09-20 , DOI: 10.1088/2057-1976/ac251f
Ping Fan 1 , Congling Yang 1, 2 , Li Wang 1 , Qiling Wang 1 , Yan Zhang 3 , Jie Zhou 1 , Jie Weng 1 , Bo Feng 1
Affiliation  

Melanoma is one of the most aggressive skin cancers. However, there remain many limitations in the current clinical treatments of it. Zinc oxide nanoparticles (ZnO NPs) have been considered to be a promising antitumor drug due to their excellent biocompatibility, biodegradability and biofunctionality. In this study, we prepared spherical ZnO NPs with an average diameter of less than 10 nm by a simple chemical method. According to the in vitro cytotoxicity assay, ZnO NPs in a certain concentration range (20–35 μg ml−1) showed significant cytotoxicity to B16F10 melanoma cells, while having little effect on the viability of 3T3L1 fibroblasts. When cultured with B16F10 melanoma cells, ZnO NPs induced the generation of reactive oxygen and mitochondrial superoxide through the release of Zn2+, leading to oxidative stress in the cells, further reducing the mitochondrial membrane potential and decreasing the number of mitochondrial cristae. Furthermore, damaged mitochondria induced the release of apoptosis factors to promote cell apoptosis. FITC-Annexin V/propidium iodide double staining assay was used to analyze different apoptosis stages of B16F10 cells induced by ZnO NPs. A polymer hydrogel (Gel-F127-ZnO NPs) with Pluronic F127 as the carrier of ZnO NPs was fabricated for evaluating the antitumor effect of ZnO NPs in vivo. The in vivo experiment indicated that the tumor recurrence was significantly inhibited in tumor-bearing mice after treated with Gel-F127-ZnO NPs. Conclusively, ZnO NPs showed a strong antitumor effect both in vitro and in vivo.



中文翻译:

ZnO 纳米颗粒刺激氧化应激诱导 B16F10 黑色素瘤细胞凋亡:体外和体内研究

黑色素瘤是最具侵袭性的皮肤癌之一。然而,目前对其临床治疗仍存在诸多局限。氧化锌纳米粒子(ZnO NPs)因其优异的生物相容性、生物降解性和生物功能性而被认为是一种很有前途的抗肿瘤药物。在这项研究中,我们通过简单的化学方法制备了平均直径小于 10 nm 的球形 ZnO NPs。根据体外细胞毒性试验,ZnO NPs 在一定浓度范围内(20-35 μ g ml -1) 对 B16F10 黑色素瘤细胞显示出显着的细胞毒性,而对 3T3L1 成纤维细胞的活力几乎没有影响。当与B16F10黑色素瘤细胞一起培养时,ZnO NPs通过释放Zn 2+诱导活性氧和线粒体超氧化物的产生,导致细胞发生氧化应激,进一步降低线粒体膜电位,减少线粒体嵴的数量。此外,受损的线粒体诱导细胞凋亡因子的释放,从而促进细胞凋亡。FITC-Annexin V/碘化丙啶双染法用于分析ZnO NPs诱导的B16F10细胞不同凋亡阶段。制备了以 Pluronic F127 为 ZnO NPs 载体的聚合物水凝胶 (Gel-F127-ZnO NPs),用于评估 ZnO NPs 的抗肿瘤作用在体内体内实验表明,经 Gel-F127-ZnO NPs 处理后,荷瘤小鼠的肿瘤复发得到显着抑制。结论是,ZnO NPs在体外体内都表现出很强的抗肿瘤作用。

更新日期:2021-09-20
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