Evaluating the anti-cancer effects of SPION-TMC-HA nanoparticles loaded with siRNA molecules against CD73 and VEGF in 4T1, CT26 and B16-F10 cell lines

Abstract

Many immunosuppressive factors are present in the tumor microenvironment that prevent the success of cancer immunotherapy. Among them, high concentration of adenosine due to high expression of CD73 molecule is one of the most important factors in suppressing anti-tumor immune responses. Increasing adenosine increasingly induces the expression of factors affecting tumor growth such as VEGF, which plays an important role in the process of angiogenesis and thus the progression of cancer. Therefore, in this study, we decided to prevent tumor progression by simultaneously inhibiting CD73 and VEGF factors. Materials and Methods: In order to inhibit the expression of CD73 and VEGF genes in mouse cell lines 4T1, CT26 and B16-F10, we used superparamagnetic iron oxide (SPION) nanocarriers loaded with siRNA. In addition, in order to increase the performance efficiency of iron oxide nanoparticles, tube chitosan and trimethyl chitosan were used to enclose them. After cell treatment, the effect of treatment on genes affecting survival, angiogenesis and metastasis was investigated by real-time PCR. Results: The results of the study showed that the nanocarriers had a size of about 133 nm, with a dispersion coefficient of less than 0.3 and a zeta potential of about 25. The nanoparticles had good physicochemical properties and could significantly suppress the expression of CD73 and VEGF factors in all three cell lines, which led to a decrease in the expression of genes involved in proliferation, colonization, migration and angiogenesis in cancer cells.