SnO(2)-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway.
SnO(2)-Doped ZnO/Reduced Graphene Oxide Nanocomposites: Synthesis, Characterization, and Improved Anticancer Activity via Oxidative Stress Pathway.
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DOI：
10.2147/ijn.s285392
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发表时间：
2021
影响因子：
8
通讯作者：
Alhadlaq HA
中科院分区：
文献类型：
--
作者：
Ahamed M;Akhtar MJ;Khan MAM;Alhadlaq HA
治疗选择性和耐药性是癌症治疗中的关键问题。目前，氧化锌纳米颗粒（ZnO NP）由于其可调节的物理化学性质，有望解决这一问题。这项工作旨在制备 SnO2 掺杂的 ZnO 纳米颗粒/还原氧化石墨烯纳米复合材料（SnO2-ZnO/rGO NCs），与纯 ZnO 纳米颗粒相比，该复合材料具有增强的抗癌活性和更好的生物相容性。通过简便的水热法制备了纯 ZnO NP、SnO2 掺杂 ZnO (SnO2-ZnO) NP 和 SnO2-ZnO/rGO NC。采用场发射透射电子显微镜 (FETEM)、能量色散光谱 (EDS)、场发射扫描电子显微镜 (FESEM)、X 射线衍射 (XRD)、紫外可见 (UV-VIS) 光谱仪和动态光散射 (DLS) 技术对制备的样品进行表征。在人乳腺癌 (MCF-7) 和人正常乳腺上皮 (MCF10A) 细胞中评估了制备样品的选择性和抗癌活性。通过氧化应激途径探讨了制备样品的抗癌活性的可能机制。 SnO2-ZnO/rGO NCs 的 XRD 谱证实了六方纤锌矿 ZnO 单相的形成。高分辨率 TEM 和 SEM 图显示 SnO2 和 rGO 在 ZnO NP 中均匀分布，具有高质量的晶格条纹，没有任何变形。与 SnO2-ZnO NP 和纯 ZnO NP 相比，SnO2-ZnO/rGO NC 的带隙能较低。 SnO2-ZnO/rGO NCs 对 MCF-7 癌细胞表现出比 SnO2-ZnO NPs 和 ZnO NPs 显着更高的抗癌活性。 SnO2-ZnO/rGO NCs 通过上调 caspase-3 基因和消耗线粒体膜电位来诱导细胞凋亡反应。机理研究表明SnO2-ZnO/rGO NCs通过氧化应激途径杀死癌细胞。此外，与 SnO2-ZnO NP 和 ZnO NP 相比，SnO2-ZnO/rGO NCs 对正常乳腺上皮（MCF10A 细胞）的生物相容性也更高。 SnO2-ZnO/rGO NCs 比 SnO2-ZnO NPs 和纯 ZnO NPs 显示出增强的抗癌活性和更好的生物相容性。这项工作提出了一种提高 ZnO NPs 选择性和抗癌活性的新方法。进一步有必要在动物模型中研究 SnO2-ZnO/rGO NC 的抗肿瘤活性。
Therapeutic selectivity and drug resistance are critical issues in cancer therapy. Currently, zinc oxide nanoparticles (ZnO NPs) hold considerable promise to tackle this problem due to their tunable physicochemical properties. This work was designed to prepare SnO2-doped ZnO NPs/reduced graphene oxide nanocomposites (SnO2-ZnO/rGO NCs) with enhanced anticancer activity and better biocompatibility than those of pure ZnO NPs. Pure ZnO NPs, SnO2-doped ZnO (SnO2-ZnO) NPs, and SnO2-ZnO/rGO NCs were prepared via a facile hydrothermal method. Prepared samples were characterized by field emission transmission electron microscopy (FETEM), energy dispersive spectroscopy (EDS), field emission scanning electron microscopy (FESEM), X-ray diffraction (XRD), ultraviolet-visible (UV-VIS) spectrometer, and dynamic light scattering (DLS) techniques. Selectivity and anticancer activity of prepared samples were assessed in human breast cancer (MCF-7) and human normal breast epithelial (MCF10A) cells. Possible mechanisms of anticancer activity of prepared samples were explored through oxidative stress pathway. XRD spectra of SnO2-ZnO/rGO NCs confirmed the formation of single-phase of hexagonal wurtzite ZnO. High resolution TEM and SEM mapping showed homogenous distribution of SnO2 and rGO in ZnO NPs with high quality lattice fringes without any distortion. Band gap energy of SnO2-ZnO/rGO NCs was lower compared to SnO2-ZnO NPs and pure ZnO NPs. The SnO2-ZnO/rGO NCs exhibited significantly higher anticancer activity against MCF-7 cancer cells than those of SnO2-ZnO NPs and ZnO NPs. The SnO2-ZnO/rGO NCs induced apoptotic response through the upregulation of caspase-3 gene and depletion of mitochondrial membrane potential. Mechanistic study indicated that SnO2-ZnO/rGO NCs kill cancer cells through oxidative stress pathway. Moreover, biocompatibility of SnO2-ZnO/rGO NCs was also higher against normal breast epithelial (MCF10A cells) in comparison to SnO2-ZnO NPs and ZnO NPs. SnO2-ZnO/rGO NCs showed enhanced anticancer activity and better biocompatibility than SnO2-ZnO NPs and pure ZnO NPs. This work suggested a new approach to improve the selectivity and anticancer activity of ZnO NPs. Studies on antitumor activity of SnO2-ZnO/rGO NCs in animal models are further warranted.