Abstract
The use of ultrasound has gained great interest for nucleic acids delivery. Ultrasound can reach deep tissues in non-invasive manner. The process of sonoporation is based on the use of low-frequency ultrasound combined with gas-filled microbubbles (MBs) allowing an improved delivery of molecules including nucleic acids in the insonified tissue. For in vivo gene transfer, the engineering of cationic MBs is essential for creating strong electrostatic interactions between MBs and nucleic acids leading to their protection against nucleases degradation and high concentration within the target tissue. Cationic MBs must be stable enough to withstand nucleic acids interaction, have a good size distribution for in vivo administration, and enough acoustic activity to be detected by echography. This review aims to summarize the basic principles of ultrasound-based delivery and new knowledge acquired in these recent years about this method. A focus is made on gene delivery by discussing reported studies made with cationic MBs including ours. They have the ability for efficient delivery of plasmid DNA (pDNA), mRNA or siRNA. Last, we discuss about the key challenges that have to be faced for a fine use of this delivery system.
Highlights
During these last two decades, chemical and physical methods have been developed at an amazing speed to improve drug/gene delivery
For in vivo gene transfer, the engineering of cationic MBs is essential for creating strong electrostatic interactions between MBs and nucleic acids leading to their protection against nucleases degradation and high concentration within the target tissue
This review aims to summarize the basic principles of ultrasound-based delivery and new knowledge acquired in these recent years about this method
Summary
During these last two decades, chemical and physical methods have been developed at an amazing speed to improve drug/gene delivery. They start oscillating at the frequency of ultrasound, under the influence of positive and negative pressure differences in the ultrasonic wave [24,25] Due to their acoustic behaviour, MBs can induce an increased surrounding cells permeability allowing drug delivery [26,27]. Several groups have reported that ultrasound application in the presence of commercial MBs can significantly enhance (more than 200-fold) gene transfer mediated by pDNA complexed with cationic lipids or polyethyleneimine (PEI) [59,60]. In this case, MBs are supposed to act on the plasma membrane to augment pDNA complexes cell uptake.
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