Study of the Mechanisms of Microbubble-Facilitated Sonoporation in vitro in Controlled Environments.

Show simple item record Fan, Zhenzhen en_US 2012-06-15T17:30:33Z NO_RESTRICTION en_US 2012-06-15T17:30:33Z 2012 en_US en_US
dc.description.abstract Successful delivery of drug molecules and therapeutic genetic materials across the plasma membrane into the target cells in sufficient dosage is important for satisfactory treatment effects. Ultrasound excitation of microbubbles generates disruption of the cell membrane (sonoporation) and opens new opportunities for non-viral intracellular drug and gene delivery. When excited by ultrasound, microbubbles undergo rapid volume expansion and contraction as well as collapse (cavitation) and can temporally disrupt the cell membrane, creating a direct physical route for the transport of extracellular agents into viable cells. However, despite increasing interest and recent progresses, challenges and difficulties remain to be overcome, including relatively low delivery efficiency and large variation in delivery outcomes. These difficulties are mainly due to the insufficient understanding of the underlying mechanisms and process of sonoporation. This study aims to obtain a comprehensive understanding of sonoporation mechanisms and process under well controlled environments. We employed various strategies to precisely control microbubbles location and cavitation, using fast-frame bright field video-microscopy combined with real-time fluorescence microscopy to reveal ultrasound excited microbubble dynamics and subsequent cellular responses, such as membrane rupture, calcium transient and waves, and gene transfection. The specific aims of this study are: 1) to investigate the intracellular transport and calcium transient generated by sonoporation; 2) to exploit dynamics activities of microbubbles driven by ultrasound and correlate with delivery outcomes; 3) to achieve controlled and enhanced delivery outcomes facilitated by targeted microbubbles. en_US
dc.language.iso en_US en_US
dc.subject Sonoporation en_US
dc.subject Microbubble en_US
dc.subject Ultrasound en_US
dc.subject Intracellular Drug and Gene Delivery en_US
dc.subject Calcium Imaging en_US
dc.title Study of the Mechanisms of Microbubble-Facilitated Sonoporation in vitro in Controlled Environments. en_US
dc.type Thesis en_US
dc.description.thesisdegreename Ph.D. en_US
dc.description.thesisdegreediscipline Biomedical Engineering en_US
dc.description.thesisdegreegrantor University of Michigan, Horace H. Rackham School of Graduate Studies en_US
dc.contributor.committeemember Deng, Cheri Xiaoyu en_US
dc.contributor.committeemember Bull, Joseph L. en_US
dc.contributor.committeemember Fowlkes, J. Brian en_US
dc.contributor.committeemember Takayama, Shuichi en_US
dc.subject.hlbsecondlevel Biomedical Engineering en_US
dc.subject.hlbtoplevel Engineering en_US
dc.owningcollname Dissertations and Theses (Ph.D. and Master's)
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