Dual target gene therapy to EML4-ALK NSCLC by a gold nanoshell-based system.

Although EML4-ALK transforming fusion gene is represented in only 8% of non-small cell lung cancer (NSCLC) cases, its expression is partly responsive for the failure of current NSCLC treatments. Preventing secondary mutation of the ALK protein through direct gene manipulation could overcome NSCLC drug resistance. In this study, we developed a gold nanoshell (HAuNs) drug carrier for delivery and selective photo-thermal release of genes that target ALK and microRNA-301 in NSCLC. Additionally, the densely-coated nanoshell adsorbed high amounts of the positively-charged anticancer drug doxorubicin (DOX), generating an exciting multidimensional treatment strategy that includes gene-, thermal- and chemo- therapy. The ALK mRNA and microRNA-301 genes as the double targets exhibited the combined effect. The drug carrier system significantly improved the drug accumulation in tumor tissues due to the enhanced vascular permeability by photothermal effect, dense spherical structure and RGD peptide modification. In vitro and in vivo results demonstrated the multiple therapeutic effects of the gold nanoshell-based system was better than the monotherapy. The above results indicated the gold nanoshell-based system would be a promising translational nano-formulation platform for effective treatment of EML4-ALK-positive NSCLC.