Efficient delivery of signal-responsive gene carriers for disease-specific gene expression via bubble liposomes and sonoporation.

Sonoporation is a promising method to intracellularly deliver synthetic gene carriers that have lower endocytotic uptake than viral carriers. Here, we applied sonoporation to deliver genes via polyethylene glycol (PEG)-grafted polymeric carriers that specifically respond to hyperactivated protein kinase A (PKA). PEG-grafted polymeric carrier/DNA polyplexes were not efficiently delivered into cells via the endocytotic pathway because of the hydrophilic PEG layer surrounding the polyplexes. However, the delivery of polyplexes into cells was significantly increased by sonoporation. The delivered polyplexes exhibited PKA-responsive transgene expression in PKA-overexpressing cells, but not in cells with low PKA activation. These results show that the sonoporation-mediated delivery of PEG-modified PKA-responsive polyplexes is a promising approach for safely applying gene therapy to abnormal cells with hyperactivated PKA.