Localized RNA interference therapy to eliminate residual lung cancer after incomplete microwave ablation

BACKGROUND: This study evaluated the safety and efficacy of localized injection of polyethylene glycol (PEG)-hyperbranched polyethyleneimine (PEI)-EGFR-small interfering RNA (siRNA) nanocomposites as a treatment for residual lung cancer after incomplete microwave ablation (MWA). METHODS: Human lung cancer cell lines with high and low EGFR expression were selected for the study. The effects of PEG-PEI-EGFR-siRNA nanocomposite transfection on the proliferation, migration, and apoptosis of lung cancer cells were verified. Sixteen healthy ICR mice were injected into the lung to test the biological safety of the nanocomposites. In addition, 24 subcutaneous xenograft BALB/C nude mice with high EGFR expression were separated into four groups and then treated with an intratumoral injection of PEG-PEI-EGFR-siRNA, PEG-PEI-normal control (NC)-siRNA, PEG-PEI-EGFR-siRNA after MWA, or PEG-PEI-NC-siRNA after MWA. Tumor growth, pathological changes, and EGFR expression in each group were observed. RESULTS: PEG-PEI-EGFR-siRNA nanocomposites were transfected to HCC 827 cells showing high EGFR expression and to H23 cells showing low EGFR expression. In HCC827 cells, downregulation of EGFR gene expression reduced cell proliferation, invasion, and migration, whereas cell apoptosis increased. In contrast, in H23 cells, no significant differences in those parameters were detected. No acute toxicity occurred in the ICR mice during the biosafety test. Localized injection of PEG-PEI-EGFR-siRNA nanocomposites significantly inhibited the growth of human lung xenografts in mice and the growth of residual tumors after MWA. CONCLUSION: PEG-PEI-EGFR-siRNA nanocomposites may be a supplemental therapy strategy to treat residual lung cancer after incomplete MWA.