Investigating the effect of trimethyl chitosan-hyaluronate nanoparticles loaded with siRNA molecules against STAT3 and CD47 in 4T1 (breast cancer) and B16-F10 (melanoma) cancer cells

Abstract

The success and efficiency of various modern immunotherapy methods are highly influenced by the tumor microenvironment. The presence of various immunosuppressive factors in the tumor microenvironment is one of the most important factors in the failure of modern treatments. STAT3 and CD47 are the most important factors present in the tumor microenvironment that have high expression and facilitate tumor growth and expansion and inhibit anti-tumor immune responses. Therefore, in this study, it was decided to inhibit the expression of these molecules in cancer cells as a new combination therapy. Materials and Methods: This study was performed on two mouse cell lines of breast cancer (4T1) and melanoma (B16-F10). Inhibition of STAT3 and CD47 molecules was performed using siRNA-loaded nanoparticles. The effect of combination therapy on cancer cells was determined by MTT assay and expression of target molecules using real-time PCR test. Results: The results showed that the synthesized nanoparticles had good physicochemical properties that facilitated their entry into cancer cells. Also, the entry of nanoparticles into cancer cells significantly inhibited the expression of STAT3 and CD47 molecules. In addition, suppressing the expression of these two factors induced cell death in cancer cells. This combination therapy could also suppress the expression of factors influencing the growth and spread of cancer.