Ultrasound molecular imaging-guided tumor gene therapy through dual-targeted cationic microbubbles†

Abstract

The success of gene therapy depends largely on the development of gene vectors and effective gene delivery systems. It has been demonstrated that cationic microbubbles can be loaded with negatively charged plasmid DNA and thus improve gene transfection efficiency. In this study, we developed dual-targeting cationic microbubbles conjugated with iRGD peptides(Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys)) and CCR2 (chemokine (C–C motif) receptor 2) antibodies (MB_iRGD/CCR2) for ultrasound molecular imaging and targeted tumor gene therapy. The ultrasound molecular imaging experiments showed that there were significantly enhanced ultrasound molecular imaging signals in the tumor that received MB_iRGD/CCR2, compared with those that received MB_iRGD, MB_CCR2, or MB_control. As a therapy plasmid, pGPU6/GFP/Neo-shAKT2, carrying an expression cassette for the human AKT2 RNA interference sequence, was used. Our results demonstrated that MB_iRGD/CCR2 had a significantly higher gene transfection efficiency than MB_iRGD, MB_CCR2, or MB_control under ultrasound irradiation, resulting in much lower AKT2 protein expression and stronger tumor growth inhibition effects in vivo and in vitro. In conclusion, our study demonstrated a novel gene delivery system via MB_iRGD/CCR2 for ultrasound molecular-imaging-guided gene therapy of breast cancer.