Targeting FGFR genes for treatment of lung cancer via siRNA loaded non-viral vectors

In this study, the FGFR1 gene was targeted with liposomes, which are non-viral vectors loaded with MNPCA nanoparticles together with FGFR1 siRNA. In the first step, nanoparticles were synthesized, coated with citric acid, their magnetic properties were examined, and FTIR and XRD characterizations were made. In the second step, the antimicrobial and antioxidant activities of the synthesized magnetic nanoparticles were investigated. In the final step, liposomes were formed and visualized by SEM. MNPCA and siRNA-loaded liposomes to target FGFR1 mRNAs were constructed and tested on the lung cancer A549 cell line. Within the scope of targeting, studies were carried out to determine cytotoxicity, apoptosis and the amount of ROS. According to the obtained characterization results, it was determined that iron oxide nanoparticles were synthesized and coated with citric acid. The aggregation of the synthesized nanoparticles on the side of the magnet showed that they have magnetic properties. However, the synthesized MNPCAs did not show any activity in terms of antimicrobial and antioxidant. At the last step, the spherical structure of the liposomes was determined with the SEM image. Liposomes loaded with MNPCA_siRNA were observed to be cytotoxic on the A549 cell line, showed a dose-dependent increase in cytotoxic activity, and the IC50 value was calculated as 46.86 ng/mL. As a result of the apoptosis study, it was determined that the A549 cell line, which was applied MNPCA_siRNA loaded liposome, underwent apoptosis. As a result of the ROS quantification study, a significant decrease in the amount of ROS was observed in the A549 cell line to which MNPCA_siRNA loaded liposomes were applied, compared to the control. In this case, it is thought that ROS is not effective on the decrease in the viability of the cell line to which MNPCA_siRNA loaded liposomes are applied. Accordingly, at the post-transcriptional level, FGFR1 mRNA is thought to be blocked by liposomes loaded with MNPCA_siRNA. As a result, MNPCA_siRNA-loaded liposomes are thought to be successfully transfected into the lung cancer A549 cell line and show its effect without any increase in ROS, which is due to a post-transcriptional interference.