Department of Oncology, Yueyang Central Hospital, Yueyang, Hunan 414000, China.
Department of Oncology, Yueyang Central Hospital, Yueyang, Hunan 414000, China.
J Trace Elem Med Biol. 2024 Jul;84:127437. doi: 10.1016/j.jtemb.2024.127437. Epub 2024 Mar 20.
Bimetallic nanoparticles, specifically Zinc oxide (ZnO) and Silver (Ag), continue to much outperform other nanoparticles investigated for a variety of biological uses in the field of cancer therapy. This study introduces biosynthesis of bimetallic silver/zinc oxide nanocomposites (Ag@ZnO NCs) using the Crocus sativus extract and evaluates their anti-cancer properties against cervical cancer.
The process of generating bimetallic nanoparticles (NPs), namely Ag@ZnO NCs, through the utilization of Crocus sativus extract proved to be uncomplicated and eco-friendly. Various methods, such as UV-vis, DLS, FTIR, EDX, and SEM analyses, were utilized to characterize the generated Ag@ZnO NCs. The MTT assay was employed to assess the cytotoxic properties of biosynthesized bimetallic Ag@ZnO NCs against the HeLa cervical cancer cell line. Moreover, the impact of Ag@ZnO NCs on HeLa cells was assessed by examining cell survival, ROS production, MMP levels, and induced apoptosis. Through western blot analysis, the expression levels of the PI3K, AKT, mTOR, Cyclin D, and CDK proteins seemed to be ascertained. Using flow cytometry, the cancer cells' progression through necrosis and apoptosis, in addition to the cell cycle analysis, were investigated.
Bimetallic Ag@ZnO NCs that were biosynthesized showed a high degree of stability, as demonstrated by the physicochemical assessments. The median size of the particles in these NCs was approximately 80-90 nm, and their zeta potential was -14.70 mV. AgNPs and ZnO were found, according to EDX data. Further, Ag@ZnO NCs hold promise as a potential treatment for cervical cancer. After 24 hours of treatment, a dosage of 5 µg/mL or higher resulted in a maximum inhibitory effect of 58 ± 2.9. The concurrent application of Ag/ZnO NPs to HeLa cells resulted in elevated apoptotic signals and a significant generation of reactive oxygen species (ROS). As a result, the bimettalic Ag@ZnO NCs treatment has been recognized as a chemotherapeutic intervention by inhibiting the production of PI3K, AKT, and mTOR-mediated regulation of propagation and cell cycle-regulating proteins.
The research yielded important insights into the cytotoxic etiology of biosynthesized bimetallic Ag@ZnO NCs against HeLa cells. The biosynthesized bimetallic Ag@ZnO NCs have a significant antitumor potential, which appears to be associated with the development of oxidative stress, which inhibits the development of the cell cycle and the proliferation of cells. Therefore, in the future, biosynthesized bimetallic Ag@ZnO NCs may be used as a powerful anticancer drug to treat cervical cancer.
双金属纳米粒子，特别是氧化锌（ZnO）和银（Ag），在癌症治疗领域的各种生物应用中继续优于其他被研究的纳米粒子。本研究采用藏红花提取物合成双金属银/氧化锌纳米复合材料（Ag@ZnO NCs），并评价其对宫颈癌的抗癌特性。
利用藏红花提取物生成双金属纳米粒子（NPs），即 Ag@ZnO NCs 的过程简单且环保。采用紫外-可见分光光度法（UV-vis）、动态光散射（DLS）、傅里叶变换红外光谱（FTIR）、能谱（EDX）和扫描电子显微镜（SEM）等多种方法对生成的 Ag@ZnO NCs 进行了表征。采用 MTT 法评估生物合成的双金属 Ag@ZnO NCs 对 HeLa 宫颈癌细胞系的细胞毒性。此外，通过检测细胞存活率、ROS 产生、MMP 水平和诱导凋亡来评估 Ag@ZnO NCs 对 HeLa 细胞的影响。通过 Western blot 分析，似乎可以确定 PI3K、AKT、mTOR、Cyclin D 和 CDK 蛋白的表达水平。通过流式细胞术，研究了癌细胞通过坏死和凋亡的进展，以及细胞周期分析。
双金属 Ag@ZnO NCs 的生物合成表现出高度的稳定性，这一点可以通过物理化学评估来证明。这些 NCs 中颗粒的中值尺寸约为 80-90nm，其 zeta 电位为-14.70mV。根据 EDX 数据，发现了 AgNPs 和 ZnO。此外，Ag@ZnO NCs 有望成为宫颈癌的潜在治疗方法。治疗 24 小时后，5μg/mL 或更高剂量可产生 58±2.9%的最大抑制作用。Ag/ZnO NPs 同时应用于 HeLa 细胞会导致凋亡信号的增加和活性氧（ROS）的显著产生。因此，双金属 Ag@ZnO NCs 治疗被认为是一种通过抑制 PI3K、AKT 和 mTOR 介导的增殖和细胞周期调节蛋白的产生来抑制细胞生长的化学疗法。
本研究深入了解了生物合成的双金属 Ag@ZnO NCs 对 HeLa 细胞的细胞毒性病因。生物合成的双金属 Ag@ZnO NCs 具有显著的抗肿瘤潜力，这似乎与氧化应激的发展有关，氧化应激抑制了细胞周期的发展和细胞的增殖。因此，在未来，生物合成的双金属 Ag@ZnO NCs 可能被用作治疗宫颈癌的强大抗癌药物。
