Suppression of tumor growth in lung cancer xenograft model mice by a poly (sorbitol-co-PEI)-mediated delivery of osteopontin siRNA

Abstract

Small interfering RNA (siRNA) represents a promising strategy for treating disease such as cancer, however, specific gene silencing requires an effective delivery system in order to overcome instability and low transfection efficiency of siRNAs. To address this issue, a polysorbitol-based transporter (PSOT) was prepared by low molecular weight branched polyethylenimine (BPEI) crosslinked with sorbitol diacrylate (SDA) and adopted for therapeutic delivery to the osteopontin (OPN) gene which is highly associated with non-small cell lung cancer (NSCLC). Characterization study confirmed that PSOT formed compact complexes with siOPN and protected siOPN against RNase. PSOT/siOPN complexes demonstrated in vitro low cytotoxicity and enhanced transfection efficiency, suggesting that this carrier could be suitable for gene silencing. In A549 and H460 lung cancer cell lines, PSOT/siOPN complexes demonstrated significant silencing efficiency at both RNA and protein levels. To study in vivo tumor growth suppression, two lung cancer cell-xenografted mice models were prepared. siOPN- treated groups demonstrated significantly reduced OPN expression at both RNA and protein levels as well as suppression of tumor volume and weight. Taken together, siOPN delivery combined with a new polymeric carrier may present a novel therapeutic biomacromolecule for lung cancer therapy.