心脏病,癌症 z-bo 2020-12-18 337

　　Recently, an article published in the Proceedings of the National Academy of Sciences pointed out that combining ultrasound energy and ultrasound microbubbles to punch holes in cells may become a new tool in the fight against cardiovascular diseases and cancer. Researchers at the University of Pittsburgh call this gene therapy method the sonohole effect therapy.

　　 To put it simply, we call the biophysical mechanism by which ultrasound triggers the rupture of cell membranes as the acoustic hole effect. The research on the sound control effect is mainly related to the physical stimulation of ultrasonic microbubble vibration and the resulting cell membrane permeability. Studies have proved that there is a shear stress threshold caused by microbubble oscillation, about 1 kPa. When the pressure exceeds this value, the permeability of the endothelial cell membrane increases. The shear stress threshold shows an inverse square root relationship with the number of oscillation cycles and the ultrasonic frequency from 0.5 Hz to 2 Hz. In addition, the real-time three-dimensional confocal microscope measurement proves that a sound hole effect process is directly caused by the apex and basal cell membrane layer to be encapsulated along the outside (sealing time<2 minutes) to directly cause the cells to form membrane holes immediately. The sonoporation effect also has great potential in cell fusion. It can fuse two adjacent cells within 30-60 minutes. Dr. Brandon Helfield, a researcher at UPMC’s Ultrasound Molecular Imaging and Therapy Center, said: “Researchers use ultrasound energy and small bubbles to selectively open a small hole in the cell for drug delivery. Using focused ultrasound beams, we can keep healthy While organizing, accurately deliver drugs to the lesion. We focus on studying the role of biophysics in this area, and improve this diagnostic method by improving technology."

　　In current gene therapy methods, researchers usually use viruses to bring genes into cells for cultivation. This method can produce strong side effects, such as immune system reactions. To solve this problem, researchers have developed gene-carrying microbubbles in blood vessels. These microbubbles can release their own genes in a targeted manner through focused ultrasound energy.

　　 Researchers at the University of Pittsburgh have developed a 25 million frames per second super-speed imaging camera, which is the only one in North America. With the help of this camera, researchers can better study the biophysical phenomena of acoustic holes. They determined the minimum local shear force required for targeted targeted therapy after the air bubble passed through the cell membrane.

　　 Xu Caichen, an associate professor of medicine at the University of Pittsburgh, developed the camera system together with the Institute of Heart, Lung, and Blood Vessels at the University of Pittsburgh. He said: "Through the ultra-speed imaging camera, we can see that bubbles can vibrate millions of times per second, enabling us to determine that the shear stress caused by microbubbles is a key factor in the acoustic hole effect. This information is also conducive to the intelligence of the treatment plan. Chemical design and preparation of microbubbles, so that we can know in advance the expected effect after opening the cells. This also gives us a starting point: to study how the cells respond to this treatment."

　　 Researchers believe that these findings will help them understand the principle of the acoustic hole effect. Help experts set appropriate parameters, including ultrasound amplitude level and microbubble design, to achieve the final clinical application. "It is very important for us to understand the biophysical mechanism of the acoustic hole effect, which can help us transform this method into an effective gene or drug delivery tool. On the basis of the PNAS research, we continue to study the acoustic hole How does the effect affect the function of the treated cells. Research and develop strategies to maximize its therapeutic effect." said Professor Flordeliza Villanueva, director of the Center for Ultrasound Molecular Imaging and Therapeutics.