Gene interfered-ferroptosis therapy of cancer

Abstract

Although some effective therapies have been available for cancer, it still poses a great threat to human health and life due to its drug resistance and low response in patients. Here, we developed a novel therapy named as gene interfered-ferroptosis therapy (GIFT) by combining iron nanoparticles and cancer-specific gene interference. Using a promoter consisted of a NF-{kappa}B decoy and a minimal promoter (DMP), we knocked down the expression of two iron metabolism-related genes (FPN and Lcn2) selectively in cancer cells. At the same time, we treated cells with Fe3O4 nanoparticles. As a result, a significant ferroptosis was induced in a wide variety of cancer cells representing various hematological and solid tumors. However, the same treatment had no effect on normal cells. By using AAV and PEI-coated Fe3O4 nanoparticles as gene vectors, we found that the tumor growth in mice could be also significantly inhibited by the intravenously injected GIFT reagents. By detecting ROS, iron content and gene expression, we confirmed that the mechanism underlying the therapy is gene inference-enhanced ferroptosis.