King Abdullah Institute for Nanotechnology, King Saud University, Riyadh 11451, Saudi Arabia.
Department of Physics and Astronomy, College of Science, King Saud University, Riyadh 11451, Saudi Arabia.
Int J Nanomedicine. 2021 Jan 8;16:89-104. doi: 10.2147/IJN.S285392. eCollection 2021.
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 SnO-doped ZnO NPs/reduced graphene oxide nanocomposites (SnO-ZnO/rGO NCs) with enhanced anticancer activity and better biocompatibility than those of pure ZnO NPs.
Pure ZnO NPs, SnO-doped ZnO (SnO-ZnO) NPs, and SnO-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 SnO-ZnO/rGO NCs confirmed the formation of single-phase of hexagonal wurtzite ZnO. High resolution TEM and SEM mapping showed homogenous distribution of SnO and rGO in ZnO NPs with high quality lattice fringes without any distortion. Band gap energy of SnO-ZnO/rGO NCs was lower compared to SnO-ZnO NPs and pure ZnO NPs. The SnO-ZnO/rGO NCs exhibited significantly higher anticancer activity against MCF-7 cancer cells than those of SnO-ZnO NPs and ZnO NPs. The SnO-ZnO/rGO NCs induced apoptotic response through the upregulation of caspase-3 gene and depletion of mitochondrial membrane potential. Mechanistic study indicated that SnO-ZnO/rGO NCs kill cancer cells through oxidative stress pathway. Moreover, biocompatibility of SnO-ZnO/rGO NCs was also higher against normal breast epithelial (MCF10A cells) in comparison to SnO-ZnO NPs and ZnO NPs.
SnO-ZnO/rGO NCs showed enhanced anticancer activity and better biocompatibility than SnO-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 SnO-ZnO/rGO NCs in animal models are further warranted.
治疗的选择性和耐药性是癌症治疗中的关键问题。目前，氧化锌纳米粒子（ZnO NPs）由于其可调节的物理化学性质，具有很大的应用潜力来解决这个问题。本工作旨在制备比纯 ZnO NPs 具有更高抗癌活性和更好生物相容性的 SnO 掺杂 ZnO NPs/还原氧化石墨烯纳米复合材料（SnO-ZnO/rGO NCs）。
通过简便的水热法制备纯 ZnO NPs、SnO 掺杂 ZnO（SnO-ZnO） NPs 和 SnO-ZnO/rGO NCs。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）、紫外可见分光光度计（UV-VIS）和动态光散射（DLS）技术对制备的样品进行了表征。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抗癌活性的可能机制。
SnO-ZnO/rGO NCs 的 XRD 谱图证实了单相六方纤锌矿 ZnO 的形成。高分辨率 TEM 和 SEM 映射显示 SnO 和 rGO 在 ZnO NPs 中均匀分布，具有高质量的晶格条纹，没有任何扭曲。与 SnO-ZnO NPs 和纯 ZnO NPs 相比，SnO-ZnO/rGO NCs 的能带隙能量更低。SnO-ZnO/rGO NCs 对 MCF-7 癌细胞的抗癌活性明显高于 SnO-ZnO NPs 和 ZnO NPs。SnO-ZnO/rGO NCs 通过上调 caspase-3 基因和耗尽线粒体膜电位诱导细胞凋亡反应。机制研究表明，SnO-ZnO/rGO NCs 通过氧化应激途径杀死癌细胞。此外，与 SnO-ZnO NPs 和 ZnO NPs 相比，SnO-ZnO/rGO NCs 对正常乳腺上皮（MCF10A 细胞）的生物相容性也更高。
SnO-ZnO/rGO NCs 比 SnO-ZnO NPs 和纯 ZnO NPs 具有更高的抗癌活性和更好的生物相容性。本工作为提高 ZnO NPs 的选择性和抗癌活性提供了一种新方法。进一步需要在动物模型中研究 SnO-ZnO/rGO NCs 的抗肿瘤活性。
