Cosilencing of CD73 and ZEB1 molecules in murine 4T1 breast cancer cells in order to suppress cancer cell growth and development

Abstract

Abnormal expression of several factors within tumor milieu helps the development of neoplasia and immune suppression in various cancers. ZEB-1 and CD73 are important factors in tumor progression, which their overexpression in tumor site enhances several cancer hallmarks, including proliferation, angiogenesis, metastasis, migration, and invasion. In this study, we decided to inhibit the expression of these factors in the tumor site by using RGD-conjugated chitosan lactate (RGD-CL) nanoparticles (NPs) encapsulating CD73/ZEB-1 siRNA molecules, in vitro and in vivo. The results showed that RGD-conjugated NPs could effectively transfect cancer cells through interaction with αvβ3 integrins expressed on cancer cells and tumoral endothelial cells, leading to suppression of target molecules and attenuation of cancer cell growth, in vitro. Moreover, the administration of these NPs led to tumor regression and attenuated angiogenesis in ovo. These findings highlight the importance of combined targeting CD73 and ZEB-1 in cancer treatment shortly in cancer patients.