Ultrasound image-guided cancer gene therapy using iRGD dual-targeted magnetic cationic microbubbles

The gene therapy attracted more and more attention for the tumor therapy. To obtain a safe gene therapy system, the new gene vectors beyond the virus were developed for a high gene therapy efficiency. The ultrasound mediated gene therapy was safer and the plasmid DNA could be delivered by the microbubbles and combined with the ultrasound to increase the gene transfection efficiency. In this work, the cationic microbubbles decorated with Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-AspCys) (iRGD peptides) and magnetic Fe₃O₄ nanoparticles (MB_iM) was designed for targeted ultrasound contrast imaging guided gene therapy of tumors. The ultrasound image intensity was dramatically enhanced at the tumor site that received MB_iM with the magnet applied, compared to those administrated the non-targeted microbubbles (MB_b) or the microbubbles with only one target material on the surface (MB_M and MB_bi). The pGPU6/GFP/Neo-shAKT2 was used as a sample gene, which down regulate the AKT2 protein expression for the cancer therapy. It illustrated that MB_iM/AKT2 had the highest gene transfection efficiency in the studied microbubbles mediated by the ultrasound, leading to the AKT2 protein expression downregulation and the strongest tumor killing effect in vitro and in vivo. In summary, a novel and biocompatible gene delivery platform via MB_iM with both the endogenous and external targeting effects for breast cancer theranostics was developed.