超声基因治疗 z-bo 2020-09-23 373

　　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. I pointed it out. 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 relationship between the number of vibration cycles and the ultrasonic frequency from 0.5 Hz to 2 Hz and the reciprocal of the square root. In addition, through real-time three-dimensional confocal microscopy measurement, the acoustic hole effect process will cause cells to directly pass through the upper basal cell membrane layer to form membrane holes (sealing time u003c2 minutes). The sonoporation effect also has great potential in cell fusion, which can make two adjacent cells fuse within 30-60 minutes.

　　Dr. Brandon Hellfield, a researcher at the UPMC Ultrasound Molecular Imaging and Therapy Center, said: “Researchers use ultrasound energy and small bubbles to selectively pierce cells for drug delivery. Use a focused ultrasound beam while maintaining healthy tissue. Accurate drug delivery Go to the lesion, focus on studying the role of biophysics in this field, and improve this diagnostic method through improved technology."

　　Current gene therapy When researchers usually use viruses to introduce genes into cells for culture, this method can cause powerful side effects, such as immune system reactions. To solve this problem, researchers have developed microbubbles that carry genes into blood vessels. The microbubbles release genes in a targeted manner through focused ultrasound energy. can do.

　　Researchers at the University of Pittsburgh have developed an ultra-high-speed image camera with 25 million frames per second. This is the only camera in North America. 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 and the University of Pittsburgh Heart, Lung and Vascular Institute jointly developed the camera system. "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 the main factor of the acoustic hole effect. This information is also available. Through chemical design and micro Bubble preparation can know in advance the expected effect after opening the cells, thereby improving the intelligence of the treatment plan. This is also the way the cells go through this process. This is also the starting point for studying how to respond."

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

　　"It is very important to understand the biophysical mechanism of the sonoporation effect. This will help transform the method into an effective gene or drug delivery tool. Research based on PNAS research. "How ultrasonic treatment affects the cell function after treatment. Research and develop strategies to maximize the effectiveness of treatment. ", Director of Ultrasound Molecular Imaging and Therapy Center. Professor Frodeliza Villanueva said.