Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, 1949635881 Tehran, Iran.
Department of Chemistry, Faculty of Pharmaceutical Chemistry, Tehran Medical Sciences, Islamic Azad University, 1913674711 Tehran, Iran.
ACS Appl Bio Mater. 2023 Sep 18;6(9):3768-3777. doi: 10.1021/acsabm.3c00434. Epub 2023 Aug 22.
Silymarin (SM) exhibits potential therapeutic effects due to having antioxidant activity. However, the low solubility and bioavailability of SM restrict its biological performance. To overcome this limitation, this study aimed to develop a nanoformulation composed of SM and dimethyltindichloride and investigate the effect of SM-loaded Sn nanoparticles on cancer cell growth and survival. An SM-Sn complex was synthesized and then characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), EDS-MAP, dynamic light scattering (DLS), and ζ-potential analysis. After that, the SW480 colorectal cancer cell line was treated with different concentrations of SM and the SM-Sn complex. Cell viability was examined through the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, analyzing apoptosis, and live-dead assay. The lipid peroxidation rate was assessed through the measurement of thiobarbituric acid (TBA). Intracellular reactive oxygen species (ROS) level and cell population in the cell cycle were measured using a flow cytometry instrument. To evaluate the colonization ability of SW480 cells, a colony formation assay was performed. Gene expression analysis was also conducted using a real-time polymerase chain reaction (PCR) technique. The findings of this study revealed the effectiveness of the SM-Sn complex in decreasing SW480 cell viability by inducing cell death-associated mechanisms. We found that the SM-Sn complex increases intracellular ROS level and malondialdehyde (MDA) content. It was also revealed that the SM-Sn complex induces cell cycle arrest and the expression of apoptotic genes. In addition, the SM-Sn complex could effectively hinder SW480 cells from constituting colonies. We conclude that the use of tin(IV) as a scaffold for enhanced delivery of SM could be considered an efficient option for inhibiting cancer cell proliferation and survival.
水飞蓟素（SM）具有抗氧化活性，因此具有潜在的治疗效果。然而，SM 的低溶解度和生物利用度限制了其生物学性能。为了克服这一限制，本研究旨在开发一种由 SM 和二甲基二氯化锡组成的纳米制剂，并研究载有 SM 的锡纳米粒子对癌细胞生长和存活的影响。合成了 SM-Sn 配合物，然后使用 X 射线衍射（XRD）、透射电子显微镜（TEM）、傅里叶变换红外（FTIR）、EDS-MAP、动态光散射（DLS）和 ζ-电位分析对其进行了表征。然后，用不同浓度的 SM 和 SM-Sn 复合物处理 SW480 结直肠癌细胞系。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴化物（MTT）测定法检查细胞活力，分析细胞凋亡和死活测定。通过测量硫代巴比妥酸（TBA）评估脂质过氧化率。使用流式细胞仪测量细胞内活性氧（ROS）水平和细胞周期中的细胞群体。为了评估 SW480 细胞的定植能力，进行了集落形成测定。还使用实时聚合酶链反应（PCR）技术进行了基因表达分析。这项研究的结果表明，SM-Sn 复合物通过诱导与细胞死亡相关的机制，有效降低了 SW480 细胞的活力。我们发现，SM-Sn 复合物增加了细胞内 ROS 水平和丙二醛（MDA）含量。还发现，SM-Sn 复合物诱导细胞周期停滞和凋亡基因的表达。此外，SM-Sn 复合物可以有效地阻止 SW480 细胞形成集落。我们得出结论，使用锡（IV）作为增强 SM 递送的支架可以被认为是抑制癌细胞增殖和存活的有效选择。
