Poly (1-Vinyl Imidazole) Polyplexes as Novel Therapeutic Gene Carriers for Lung Cancer Therapy

Abstract

The present work explores the ability of poly (1-vinyl imidazole) to complex si-RNA against vascular endothelial growth factor (VEGF) and its in vitro efficiency in A549 lung cancer cells. The polyplex formed was found to exhibit 66% complexation efficiency. The complexation was confirmed by gel retardation assay, 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 the free si-RNA in silencing VEGF in lung cancer cells. The silencing of VEGF was quantified using Western blot which was also reflected in depletion of HIF-1a 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 polyplex reveal that the superior VEGF silencing by the polyplex altered the expression levels of several other genes that have been implicated in the proliferation and invasion of lung cancer cells. These results indicate that PVI complexed anti-VEGF can be an effective strategy to counter lung cancer.