Drug resistance against taxanes and platins is prominent in lung cancer. Targeted microRNAs and extracellular vesicles (EVs) have potential for treating resistant cancers. In this study, we used natural killer cell-derived EVs (NK-EVs) as delivery system for microRNA that regulate the expression of programmed cell death-ligand 1 (PD-L1). EVs were isolated by ultracentrifugation and characterized by NTA and BCA assay and then loaded with PD-L1-miRNA mimetic (PLM) using electroporation. Cytotoxicity studies using lung PDX and resistant H1975 cells (EGFR-L858R mutations) demonstrated that NK-EVs incorporated with PLM increased cell death (p < 0.01) 2.1-fold and 1.8-fold respectively as compared to PLM suggesting the cytotoxic potential of NK-EVs. The Balb/c nude mice bearing resistant H1975 tumors were treated with NK-EVs, PLM and NK-EVs containing PLM and the tumor volumes were 68%, 31% and 14% respectively compared to control group at the end of study. Studies are undergoing to understand the molecular mechanisms of NK-EVs.
Learning Objectives:
Upon completion, participants will be able to use natural killer (NK) cell-derived extracellular vesicles for delivering therapeutic miRNAs which regulate PD-L1 for the treatment of resistant lung cancer.
Upon completion, participants will be able to learn the process of EVs isolation from NK cells by differential ultracentrifugation, their characterization and loading the therapeutic cargo by electroporation.
Upon completion, participants will be able to conduct experiments for in-vitro and in-vivo studies to understand the potential benefits of the miRNA loaded EVs in treating resistant lung cancer.
