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EPSRC Reference: GR/T23688/01
Title: Active Probe Microscopy for Molecular Delivery to Cells: Observation, Quantitation and Control of in-vitro Bioeffect
Principal Investigator: Campbell, Dr PA
Other Investigators:
Sibbett, Professor W Rose, Professor MJ Cuschieri, Professor Sir A
Frank, Dr T Bourdon, Dr J
Researcher Co-Investigators:
Project Partners:
Department: Surgery and Oncology
Organisation: University of Dundee
Scheme: Standard Research (Pre-FEC)
Starts: 01 October 2004 Ends: 31 March 2008 Value (£): 279,822
EPSRC Research Topic Classifications:
Med.Instrument.Device& Equip.
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
Biophysical approaches are an attractive route for generic drug delivery in that they typically offer wider applicability when compared with viral or biochemical alternatives, which tend to be cell/tissue selective and often have serious side-effects. Of the handful of feasible biophysical approaches devised thus far, the use of ultrasound to mediate molecular delivery (i.e. sonoporation) has particular promise for clinical implementation as: (i) the treatment does not require open surgical access to the target tissues; (ii) therapy can be implemented using standard hospital equipment; (iii) and also exposure is localised so that a target region only is affected. Empirically, sonoporation has been successfully used to kill cells, either by direct physical lysis 111 or via initiation of programmed cell death (apoptosis) [2]. The technique has also been used to deliver molecules/therapeutics whilst retaining cell viability (reparable sonoporation) [3], thus it has applicability not only in oncological therapy, but also in gene-therapy. The mechanism of sonoporation however remains elusive, and therefore hampers attempts to optimise the technique. We do know that the efficacy of molecular uptake is enhanced considerably when commercial ultrasound contrast agent microbubbles are present during application of the ultrasound energy [4]. Cavitation processes are therefore thought to be the key to the matter: however, even then it is unclear whether or not microjetting from imploding bubbles or else membrane shearing due to microstreaming in the vicinity of oscillating bubbles, as recently demonstrated by Marmottant and Hilgenfeldt (Nature 423, 153 (2003)), is the dominant process. Moreover, either alternative, or some as yet unrecognised process, may prevail under distinct ultrasound regimes only.The aim of the present proposal is to identify the mechanism of membrane permeabilisation via an innovative use of active scanning probe microscopy coupled with simultaneous real-time fluorescence microscopy.REFERENCES[1] Ward M, Wu J & Chiu JF. J Acoust Soc Amer 105 (5) 2951 (1999) [2] Feril L et al. Ultrasound in Medicine and Biology 29 (2) 331 (2003) [3] Guzman HR & Prausnitz MR J Acoust Soc Amer 110 (1) 597 (2001) [4] Lu OL & Blomley MJK. Gene Therapy 10, 396 (2003)[5] Campbell PA et al. Inst. Phys. Conf. Series 168, 513-517 (2001)
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Organisation Website: http://www.dundee.ac.uk