Synthesis and Evaluation of the Anticancer Effects of Iron Oxide-Chitosan Magnetic Nanoparticles Loaded Atorvastatin on the Invasion and Tumorigenicity of C6 Cell Line in Glioblastoma Animal Model

Abstract

Glioblastoma multiforme is one of the most vascularized and invasive solid tumors because it constantly needs to be vascularized due to the production of angiogenic factors, including vascular endothelial growth factor and epidermal growth factor. As a result, scientists are searching for complementary, alternative, or even combination medicines with fewer adverse effects and high efficacy. One type of statin that is effective in treating some forms of cardiovascular disease is Atorvastatin, which is also recognized as a suitable therapeutic option for inhibiting the growth of angiogenesis and coronary vessel pathogenesis. In the current research, we synthesized and characterized magnetic Fe₃O₄–chitosan nanoparticles loaded with Atorvastatin (ch/Fe/ATV), and we evaluated their anti-tumor efficiency in-vivo as well as their anti-proliferative, apoptotic, and the cell cycle arrest effects on the C6 glioma cell line in-vitro. In C6 cells, it was discovered that ch/Fe/ATV was useful in inducing ROS, apoptosis-induced cell death, and suppression of proliferation. During the in-vivo stage of the study, it was shown that ch/Fe/ATV could effectively reduce tumor development and improve the survival rate of animal models of GBM. qRT-PCR findings in this study demonstrate that ch/Fe/ATV may down-regulate anti-apoptotic factors including Bcl-2, VEGF, and BDNF, which are critical factors in tumor growth, and up-regulate apoptotic factors such as BAX, Caspase 3, and p53. Additionally, we discovered that applying a magnet to the tumor site helped increase the amount of ATV doses delivered to the tumor using ch/Fe/ATV nanoparticles.

Graphical Abstract