Prussian blue nanoparticle-loaded microbubbles for photothermally enhanced gene delivery through ultrasound-targeted microbubble destruction

By adsorbing chitosan (CS)-functionalized Prussian blue (PB) nanoparticles (CS/PB NPs) complexing DNA onto the surface of gas encapsulated microbubbles (MBs), a multifunctional gene delivery system of MBs@CS/PB/DNA was fabricated for photothermally enhanced gene transfection through ultrasound-targeted microbubble destruction. CS/PB NPs of (2.69 ± 0.49) nm could complex DNA effectively when the mass ratio was 2:1. It was found that MBs@CS/PB/DNA could enhance ultrasound imaging greatly both in vitro and in vivo. In addition, MBs@CS/PB/DNA could be disrupted by applying a higher-intensity ultrasound irradiation to release CS/PB/DNA, which could effectively transform the near-infrared (NIR) light into heat to assist the uptake of CS/PB/DNA by cells. With the aid of ultrasound irradiation and NIR light irradiation, the gene transfection efficiency was significantly enhanced to (43.08 ± 1.13)%, much higher than polyethylenimine. Moreover, MBs@CS/PB/DNA showed excellent biocompatibility, encouraging the further exploration of MBs@CS/PB/DNA to be a platform for combined ultrasound image, photothermal therapy, drug delivery, and gene therapy.