Researchers devise a method that combines ultrasound energy with microbubbles to open up cells to receive therapeutic agents. The invention could lead to new cancer therapies.

Kristopher Sturgis

The new technique, known as sonoporation, was created by researchers from the University of Pittsburgh and doctors from UPMC as part of a new study that aims to explore gene therapy as a new approach in the fight against cardiovascular disease and cancer. Brandon Helfield, PhD, a postdoctoral fellow at the Center for Ultrasound Molecular Imaging and Therapeutics at UPMC and lead author on the study, says that the concept of sonoporation is surprisingly simple.

"Sonoporation is the process of using sound (sono), specifically ultrasound, to poke holes (poration) into cells by using small bubbles," Helfield says. "The passage of ultrasound energy causes gas pockets, or bubbles, to physically vibrate, compressing and expanding the surrounding environment. Following up with state-of-the-art fluorescence imaging to visualize the membranes of cells, we examined the consequences of sonoporation on neighboring cells. In doing so, we observed the nature of this perforation to be small, resealing pores within the cell membrane -- while also causing gaps between neighboring cells that open and loosen the cells to allow the delivery of therapeutics to the disease."

The technique offers an alternative approach to gene therapy that could provide a precise delivery of therapeutic agents to the cells without damaging healthy tissue. Traditional forms of gene therapy rely on viruses to deliver the genes of interest to the cells, causing inflammatory immune responses that can limit their impact. There are also non-viral approaches like needle injection and liposomal constructs, but Helfield says these methods possess their own limitations.

"Direct needle injection into the target poses challenges in achieving homogenous tissue distribution of the payload," he says. "Clinical implementation is limited by the impractical requirements of repetitive needle injections into sites which may be difficult to access. Sonoporations is a promising non-viral approach that overcomes these limitations by allowing for site-specific delivery of a targeted therapeutic. And because microbubbles are also used for diagnostic ultrasound applications, this approach has its natural extension of the possibility of image-guided therapeutic delivery."

Gene therapy solutions continue to gain momentum as the technology to edit and engineer genes and cells continues to advance. Just last year a new startup announced a new technology that could genetically engineer red blood cells, turning them into drug-delivery vehicles for hard-to-treat genetic disorders.

Similarly, sonoporation looks to improve the means to deliver drugs, specifically when it comes to the delivery of plasmid DNA, oligonucleotides, and siRNA to arteries in the heart to help reduce hyperplasia and restenosis. Helfield says that ultrasound-assisted therapies are already beginning to make an impact in other areas of medicine, and this study hopes to build on that foundation.

"Ultrasound-assisted microbubble therapies are already starting to make a big impact in clinical medicine," he said. "Clinical trials have demonstrated the technique of using ultrasound and microbubbles to break up clots (sonothrombolysis) in stroke patients, and more recently, the first clinical trial was conducted using ultrasound-stimulated microbubbles to transiently and locally increase blood-brain barrier permeability to allow entry of cancer therapeutics to brain tumors."

Helfield says that their group will continue to investigate how sonoporation affects the function of treated cells, and work toward developing new strategies to maximize its therapeutic effects. The aim is to continue to increase their understanding of how sonoporation works so the approach can be tailored towards a localized gene delivery platform for the treatment of cardiovascular disease and cancer.