Concurrent inhibition of CD73 and CD47 molecules with siRNA loaded nanoparticles in cancer cells

Abstract

Increased expression of immune response inhibitory factors and tumor progression factors are important factors in the failure of various common immunotherapy methods used to treat cancer. CD73 and CD47 factors are among the most important factors involved in the growth and spread of cancer that have a very high expression in the tumor microenvironment. These two factors interact with each other to increase the growth and spread of cancer and suppress immune responses. As a result, combined inhibition of these two factors can be an effective way to treat cancer. Materials and Methods: In this study, after physicochemical analysis of nanoparticles and determining their size, zeta potential, morphology and stability, the effect of nanoparticles loaded with siRNA molecules against CD73 and CD47 in 4T1 and B16-F10 cell lines was evaluated. Took. The effect of treatment on cell survival was assessed using MTT assay. Also, the effect of combination therapy on the expression of the desired genes was investigated using real-time PCR. Results: The results of this study showed that the produced nanoparticles have a size of about ~ 110 nm, PDI <0.2 and a zeta potential of 18 mV. Also, their morphology was spherical, with high siRNA uptake, high serum stability and low toxicity. Simultaneous inhibition of CD73 and CD47 molecules was associated with reduced cancer cell survival. In addition, it was found that genes involved in tumor growth were significantly reduced.