A near infrared fluorescent/ultrasonic bimodal contrast agent for imaging guided pDNA delivery via ultrasound targeted microbubble destruction

Abstract

This paper reported the development of a multifunctional contrast agent for near infrared (NIR) fluorescent/ultrasonic bimodal imaging and gene delivery. CuInS₂–ZnS alloyed quantum dots (ZCIS QDs) were coated with polyethyleneimine (PEI) to complex plasmid DNA (pDNA), followed by adsorption onto the surface of microbubbles (MBs) generated from the surfactant mixture of Span 60 and Tween 80. It was found that the obtained composite agent of MBs@QDs@PEI/pDNA had excellent capability to enhance both ultrasound and fluorescence imaging. In addition, an in vitro cell experiment showed that pDNA could be released from MBs@QDs@PEI/pDNA and internalized by target HeLa cells to realize a relatively high transfection efficiency by ultrasound-targeted microbubble destruction. Furthermore, the cytotoxicity, immune toxicity and histological evaluation showed that MBs@QDs@PEI/pDNA had a good biocompatibility for medical application. Therefore, such a multifunction agent could operate as a promising platform for targeting gene delivery under the guidance of NIR fluorescent/ultrasonic bimodal imaging.