Investigating the effect of nanoparticles loaded with siRNA molecules against NOTCH1 and SF3B1 in chronic lymphocytic leukemia cells on leukemic cell sensitivity to Paclitaxel

Abstract

Chemoresistance is still a significant obstacle to cancer therapy. Dysregulation of the splicing factor 3b subunit 1 (SF3B1) and NOTCH1 factors have been found frequently in chronic lymphocytic leukemia (CLL), leading to the development of chemotherapy resistance. Thus, we attempted to improve the chemosensitivity of CLL cells by blocking NOTCH1 and SF3B1. Methods: We used chitosan lactate (CL) nanoparticles (NPs) coated with anti-ROR1 antibody, and loaded with NOTCH1 and SF3B1 small interfering RNAs (siRNAs) in combination with paclitaxel (PTX) to suppress NOTCH1 and SF3B1 in peripheral blood mononuclear cells and bone marrow mononuclear cells isolated from CLL patients. We also assessed the impact of this therapeutic strategy on leukemic cell chemosensitivity. Results: The results showed that ROR-1-conjugated NPs could efficiently deliver therapeutics to leukemic cells. Moreover, NPs loaded with NOTCH1/SF3B1 siRNAs and PTX significantly suppressed NOTCH1 and SF3B1 expression, increased leukemic cell sensitivity to PTX, and decreased the proliferative capacity of leukemic cells.