Alidoust Fatemeh Azizi, Zahmatkesh Hossein, Rasti Behnam, Zamani Hojjatolah, Mirpour Mirsasan, Mirzaie Amir
Department of Microbiology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University, Lahijan, Iran.
Department of Biology, University of Guilan, Rasht, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Dec 20. doi: 10.1007/s00210-024-03724-1.
Treatment of chronic myeloid leukemia (CML) is a significant therapeutic challenge, and exploration of novel treatment approaches is an urgent necessity. This work investigates the anticancer properties of rutin-conjugated zinc oxide nanoparticles (Rut-ZnO NPs) against CML cells. Physicochemical properties of the NPs were studied by FT-IR, FE-SEM, XRD, zeta potential, and DLS analyses. The MTT, flow cytometry, and quantitative PCR assays were utilized to evaluate cell viability, apoptosis, and Bax/Bcl-2 ratio, respectively. The ZnO-Rut NPs were amorphous with an average size of 59.50 nm, and hydrodynamic size and zeta potential were 161.7nm and -34.3 mV, respectively. The ZnO-Rut NPs showed good cytocompatibility as the viability of peripheral blood mononuclear cells remained above 85% at concentrations up to 100 μg/mL. ZnO-Rut NPs reduced the viability of K562 cells from 92 to 31% at exposure concentrations from 3.125 to 400 μg/mL. The IC values for rutin, ZnO NPs, and ZnO-Rutin NPs against K562 cells were 501.8, 386.3, and 175.9 μg/mL, respectively. Following the exposure to ZnO-Rutin NPs, the percentage of early apoptosis increased slightly from 10.5% to 14.1%, and a significant increase (from 11% to 50.9%) in late apoptosis was observed. The mRNA level of the Bax elevated to 1.98 folds, and the Bcl-2 gene was downregulated to 0.33 folds, underscoring the mechanism by which ZnO-Rutin NPs promote apoptosis. This study highlights the efficient anticancer potential of ZnO-Rutin NPs against CML cells, providing the basis for further investigations into their clinical applicability and underlying mechanisms of action.
慢性粒细胞白血病（CML）的治疗是一项重大的治疗挑战，探索新的治疗方法迫在眉睫。本研究调查了芦丁共轭氧化锌纳米颗粒（Rut-ZnO NPs）对CML细胞的抗癌特性。通过傅里叶变换红外光谱（FT-IR）、场发射扫描电子显微镜（FE-SEM）、X射线衍射（XRD）、zeta电位和动态光散射（DLS）分析研究了纳米颗粒的物理化学性质。分别利用MTT法、流式细胞术和定量PCR检测评估细胞活力、凋亡情况以及Bax/Bcl-2比值。ZnO-Rut NPs为无定形，平均粒径为59.50nm，流体动力学粒径和zeta电位分别为161.7nm和-34.3mV。ZnO-Rut NPs表现出良好的细胞相容性，在浓度高达100μg/mL时外周血单个核细胞的活力仍保持在85%以上。在暴露浓度为3.125至400μg/mL时，ZnO-Rut NPs将K562细胞的活力从92%降低至31%。芦丁、ZnO NPs和ZnO-芦丁纳米颗粒对K562细胞的半数抑制浓度（IC）分别为501.8、386.3和175.9μg/mL。暴露于ZnO-芦丁纳米颗粒后，早期凋亡百分比从10.5%略有增加至14.1%，晚期凋亡显著增加（从11%增至50.9%）。Bax的mRNA水平升高至1.98倍，Bcl-2基因下调至0.33倍，这突出了ZnO-芦丁纳米颗粒促进凋亡的机制。本研究强调了ZnO-芦丁纳米颗粒对CML细胞具有高效的抗癌潜力，为进一步研究其临床适用性和潜在作用机制提供了依据。
