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Silymarin-Loaded Tin(IV) Nanoparticles Exhibit Enhanced Bioavailability and Antiproliferative Effects on Colorectal
Hossein Abbasinia1, Masoumeh Heshmati1, Mohammad Yousefi2
1Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, 1949635881 Tehran, Iran.
Abstract:
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.
