How to use ultrasound gene therapy to treat heart disease and cancer?

  A new article in the Proceedings of the National Academy of Sciences found that the combination of ultrasound energy and ultrasound microbubbles may be a new tool against cardiovascular disease and cancer.  Researchers at the University of Pittsburgh call this gene therapy sound hole effect therapy.

  Simply put, the biophysical mechanism by which ultrasound causes cell membrane rupture is called the acoustic Hall effect. The research of acoustic control effect is mainly related to the physical stimulation of ultrasonic microbubble vibration and the permeability of the cell membrane produced. Studies have shown that the threshold of shear stress caused by the vibration of microbubbles is about 1 kPa, and when the pressure exceeds this value, the permeability of the endothelial cell membrane will increase. The shear stress threshold shows the inverse square root relationship between the number of vibration cycles and the ultrasonic frequency from 0.5 Hz to 2 Hz. In addition, through real-time 3D confocal microscope measurement, the acoustic hole effect process is to encapsulate the upper and basal cell membrane layers along the outside (sealing time u003c2 minutes), which causes the cells to directly produce membrane holes. verified. The acoustic perforation effect also has great potential in cell fusion. Two adjacent cells can fuse within 30-60 minutes.

  Dr. Brandon Hellfield, a researcher at UPMC Ultrasound Molecular Imaging and Therapy Center, said: “Researchers use ultrasound energy and small bubbles to selectively open small holes in cells for drug delivery. Focused ultrasound beams are used to form healthy lesions. Organization. We can accurately administer drugs. We will focus on studying the role of biophysics in this field and improving technology to improve this diagnostic method."

  Researchers usually use viruses to bring genes into cells and culture them, which can cause powerful side effects, such as immune system reactions. To solve this problem, researchers developed microbubbles that carry genes into blood vessels. These microbubbles can release their genes in a targeted manner through focused ultrasound energy.

  Researchers at the University of Pittsburgh have developed North America’s only ultra-fast imaging camera with 25 million frames per second. With this camera, researchers can better study the biophysical phenomena in the acoustic hall. They determined the minimum local shear force required for targeted therapy after the bubble passed through the cell membrane.

  University of Pittsburgh Medical Associate Professor Xu Caichen has developed a camera system in cooperation with the University of Pittsburgh Heart, Lung and Vascular Institute. He said: Through the ultra-fast imaging camera, we can see that the bubbles vibrate millions of times per second, and can determine that the shear stress caused by the microbubbles is an important factor in the acoustic Hall effect. It also contributes to the intelligent, chemical design and preparation of microbubbles, so that you can know the expected effect after opening the cell in advance, which is also how the cell responds to this process. This is also the starting point of research. "

  These findings of the researchers are believed to help them understand the principle of the acoustic Hall effect. We help professionals to set appropriate parameters, such as ultrasound amplitude level and microbubble design, to achieve the final clinical application.

  "Understanding the biophysical mechanism of the sonoporation effect is very important. This will help transform the method into an effective gene or drug delivery tool. Based on PNAS research. How does the effect of sonication affect the cell function after treatment? Research and development can be maximized Strategies to improve the effect of chemical treatment." said Professor Frodrizza Villanueva, director of the Sonic Molecular Imaging and Therapy Center.