Investigating the effect of nanoparticles loaded with siRNA molecules against Nrf2 and cyclophosphamide on chronic lymphoid leukemia (CLL) cells

Abstract

Targeting influential factors in resistance to chemotherapy is one way to increase the effectiveness of chemotherapeutics. The erythroid 2-related factor 2 (Nrf2) pathway overexpresses in chronic lymphocytic leukemia (CLL) cells and plays a significant role in leukemic cell survival and chemotherapy resistance. Methods: Therefore, we have produced rituximab-conjugated pegylated chitosan lactate nanoparticles (RTX-CLP NPs) to deliver Nrf2 small interfering RNAs (siRNAs) to the CD20-expressing CLL cells to increase the sensitivity of leukemic cells to Cyclophosphamide (CP). Results: The findings revealed that the generated NPs had efficient physicochemical properties, were less toxic, showed controlled siRNA release, and were transfected efficiently into CLL primary cells (derived from both the peripheral blood mononuclear cells and bone marrow mononuclear cells). After treatment with rituximab-conjugated NPs, we silenced Nrf2 expression in leukemic cells, which was associated with increased sensitivity of leukemic cells to CP and decreased anti- and an increase in pro-apoptotic factors.