Development of in vivo sonoporation method using short-pulsed ultrasound with microbubbles adjacent to cells.

这项研究的最终目标是开发一种安全有效的体内超声手术方法，该方法在细胞附近存在微泡的情况下使用短脉冲超声波。开发了一种光学显微镜系统，用于对超声手术过程中产生的细胞变化进行时间推移观察，并用于研究提高超声手术效率的方法。通过改变气泡的大小和位置来控制膜损伤的位置和程度。利用该系统观察了在20分钟内发生的细胞膜损伤和修复，并对其机理进行了探讨。对观察室进行了改进，使之能够观察到超声切割引发的长期细胞变化，并将延时观察的时间延长至20小时。开发了两种功能气泡，即组织靶向气泡和载药气泡，并证实了它们对提高所提出的超声治疗方法的有效性。

The final goal of this study was to develop a safe and efficient method for in vivo sonoporation that uses short-pulsed ultrasound in the presence of microbubbles adjacent to cells. A light microscopy system was developed for time-lapse observation of changes in cells generated during sonoporation and used to study methods to improve efficiency of the sonoporation. Optical tweezers were included in the system to control the position and extent of membrane damage by changing bubble size and position. Cell membrane damage and repair, which occur in a period shorter than 20 minutes, were observed using the system and their mechanisms were investigated. The observation chamber was improved to enable observation of long-term cell changes initiated by sonoporation, and the period of time-lapse observation was extended up to 20 hours. Two types of functional bubbles, tissue-targeting bubbles and drug-loaded bubbles, were developed, and their effectiveness for improving the efficacy of the proposed sonoporation method was confirmed.