Therapeutic microbubbles for vascular drug delivery and bacterial killing

Author: Klazina Kooiman
Time: 11H00
Language: English
Place: Conference Room at LabTAU

Abstract: Ultrasound-activated vibrating microbubbles (1-10 µm in size) have shown preclinical potential to boost drug therapy and reduce side-effects for treating cardiovascular disease and cancer because drugs are delivered locally. Recently, safety of the treatment was demonstrated in several clinical trials. Despite the advances in the field, the underlying mechanism of microbubble-mediated drug delivery are poorly understood. One of the reasons for this is the huge range in time scales involved. The time scale of the microbubble vibration is 2 million times per second in a 2 MHz ultrasound field (microseconds), which is many orders of magnitude smaller than the time scale of physiological effects (milliseconds), let alone that of biological effects (seconds to minutes) and clinical relevance (days to months). To allow the investigation of the microbubble-cell-drug interaction at a microsecond and micrometer resolution, unique technology was created by coupling an ultra-high-speed camera (~20 million frames per second recordings) to a custom-built confocal microscope. In this seminar, I will describe new insights gained into the microbubble-cell-drug interaction by using this technology for two different cell types: endothelial cells that line blood vessels and bacteria. For endothelial cells, the focus will be on the microbubble behavior in relation to the drug delivery pathways sonoporation (i.e., cell membrane poration), tunnel formation and cell-cell contact opening, as well as how the cytoskeleton F-actin plays a role. Novel microbubble-mediated treatments for the life-threatening disease bacterial infective endocarditis, either on native heart valves or cardiac devices such as pacemakers, are the focus for the bacteria biofilm work.