The advent of molecular engineering has led to the development of a wide range of therapeutic agents including peptides, antibodies, adenoviruses, and nanoparticles, which are capable of slowing or reversing the course of diseases. Yet despite their demonstrated biological potency in vitro, many of these agents fail in vivo due to non-specific responses, off-target side effects, systematic clearance and insufficient delivery to the site of interest. The Non-invasive Surgery & Biopsy Laboratory aims to overcome these limitations by using mechanical forces to open the primary barrier to drug efficacy: the capillary. This talk will cover novel methods to non-invasively generate micron-sized mechanical forces deep in the body using ultrasound and systematically-administered microbubbles. It will then discuss methods for using these mechanical forces in two distinct applications. The first is the use of stable and mild levels of mechanical stress in order to safely and reversibly open the blood-brain barrier. This resulted in the first demonstration of neuronal delivery across ultrasonically-opened cerebral capillaries. The second is the use of transient and high magnitude mechanical stress in order to enhance the penetration of adenoviruses deep into the parenchyma of tumours. Using the combined potency of self-replicating viruses with the enhanced distribution by ultrasound, reduction of tumour growth rates were demonstrated. Thus the use of ultrasound and microbubbles to alter microenvironments provides a noninvasive, local, and dynamic approach to overcoming drug delivery barriers.
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Dr James J Choi, Department of Bioengineering, Imperial College London