Sendai viroplexes for epidermal growth factor receptor-directed delivery of interleukin-12 and salmosin genes to cancer cells

Background The effective delivery of therapeutic genes to target cells has been a fundamental goal in cancer gene therapy because of its advantages with respect to both safety and transfection efficiency. In the present, study we describe a tumor‐directed gene delivery system that demonstrates remarkable efficacy in gene delivery and minimizes the off‐target effects of gene transfection. Methods The system consists of a well‐verified cationic O,O′‐dimyristyl‐N‐lysyl glutamate (DMKE), Sendai virus fusion (F) protein and hemagglutinin–neuraminidase (HN) protein, referred to as cationic Sendai F/HN virosomes. To achieve tumor‐specific recognition, anti‐epidermal growth factor (EGF) receptor antibody was coupled to the surface of the virosomes containing interleukin‐12 (IL‐12) and/or salmosin genes that have potent anti‐angiogenetic functions. Results Among the virosomal formulations, the anti‐EGF receptor (EGFR) viroplexes, prepared via complexation of plasmid DNA (pDNA) with cationic DMKE lipid, exhibited more efficient gene transfection to tumor cells over‐expressing EGF receptors compared to the neutrally‐charged anti‐EGFR virosomes encapsulating pDNA. In addition, the anti‐EGFR viroplexes with IL‐12 and salmosin genes exhibited the most effective therapeutic efficacy in a mouse tumor model. Especially when combined with doxorubicin, transfection of the two genes via the anti‐EGFR viroplexes exhibited an enhanced inhibitory effect on tumor growth and metastasis in lungs. Conclusions The results of the present study suggest that anti‐EGFR viroplexes can be utilized as an effective strategy for tumor‐directed gene delivery. Copyright © 2016 John Wiley & Sons, Ltd.