Poly(1-vinylimidazole) polyplexes as novel therapeutic gene carriers for lung cancer therapy

Abstract

The present work explores the ability of poly(1-vinylimidazole) (PVI) to complex small interfering RNA (siRNA) silencing vascular endothelial growth factor (VEGF) and the in vitro efficiency of the formed complexes in A549 lung cancer cells. The polyplex formed was found to exhibit 66% complexation efficiency. The complexation was confirmed by gel retardation assays, FTIR and thermal analysis. The blank PVI polymer was not toxic to cells. The polyplex was found to exhibit excellent internalization and escaped the endosome effectively. The polyplex was more effective than free siRNA in silencing VEGF in lung cancer cells. The silencing of VEGF was quantified using Western blot and was also reflected in the depletion of HIF-1α levels in the cells treated with the polyplex. VEGF silencing by the polyplex was found to augment the cytotoxic effects of the chemotherapeutic agent 5-fluorouracil. Microarray analysis of the mRNA isolated from cells treated with free siRNA and the polyplex reveal that the VEGF silencing by the polyplex also altered the expression levels of several other genes that have been connected to the proliferation and invasion of lung cancer cells. These results indicate that the PVI complexes can be an effective agent to counter lung cancer.