Study of anti-cancer effects of inhibition of CD73 and Akt molecules by siRNA-loaded Nanoparticles

Abstract

One of the effective ways to treat cancer can be to target immune-suppressing mechanisms in the tumor microenvironment. One of these therapeutic targets is the CD73 molecule, an actoenzyme that produces adenosine, a highly inhibitory factor in the host. PI3K / Akt is an important pathway in cell growth that also plays an important role in tumorigenesis. Studies have shown that CD73 activates the PI3K / Akt signaling pathway in cells and promotes further tumor growth. Therefore, in this study, our goal was to block this reinforcing loop. Materials and Methods: In this study, hyaluronate-coated trimethyl chitosan nanoparticles were used to transfer CD73 and Akt specific siRNAs to three cancer cell lines including 4T1, CT26 and B16-F10. Results:The synthesized nanoparticles with appropriate physicochemical properties were able to significantly suppress the expression of CD73 and Akt factors in all three cell lines. Also, combination therapy was able to significantly inhibit the expression of genes involved in the growth and spread of cancer. This treatment strategy also had a high ability to suppress the migratory and metastatic features of cancer cells.