Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines

Rachel Myers,1 Megan Grundy,2 Cliff Rowe,1 Christian M Coviello,1 Luca Bau,2 Philippe Erbs,3 Johann Foloppe,3 Jean-Marc Balloul,3 Colin Story,1 Constantin C Coussios,2 Robert Carlisle2 1OxSonics Ltd, The Magdalen Centre, 2BUBBL, IBME, Department of Engineering Science, University of Oxford, Oxford,...

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Autores principales:	Myers R, Grundy M, Rowe C, Coviello CM, Bau L, Erbs P, Foloppe J, Balloul JM, Story C, Coussios CC, Carlisle R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Nanomedicine antibody virus ultrasound cavitation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c577637403ca43e89c1b3be55c5fe0f8
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spelling	oai:doaj.org-article:c577637403ca43e89c1b3be55c5fe0f82021-12-02T02:02:31ZUltrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines1178-2013https://doaj.org/article/c577637403ca43e89c1b3be55c5fe0f82018-01-01T00:00:00Zhttps://www.dovepress.com/ultrasound-mediated-cavitation-does-not-decrease-the-activity-of-small-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Rachel Myers,1 Megan Grundy,2 Cliff Rowe,1 Christian M Coviello,1 Luca Bau,2 Philippe Erbs,3 Johann Foloppe,3 Jean-Marc Balloul,3 Colin Story,1 Constantin C Coussios,2 Robert Carlisle2 1OxSonics Ltd, The Magdalen Centre, 2BUBBL, IBME, Department of Engineering Science, University of Oxford, Oxford, UK; 3Transgene SA, Illkirch-Graffenstaden, France Abstract: The treatment of cancer using nanomedicines is limited by the poor penetration of these potentially powerful agents into and throughout solid tumors. Externally controlled mechanical stimuli, such as the generation of cavitation-induced microstreaming using ultrasound (US), can provide a means of improving nanomedicine delivery. Notably, it has been demonstrated that by focusing, monitoring and controlling the US exposure, delivery can be achieved without damage to surrounding tissue or vasculature. However, there is a risk that such stimuli may disrupt the structure and thereby diminish the activity of the delivered drugs, especially complex antibody and viral-based nanomedicines. In this study, we characterize the impact of cavitation on four different agents, doxorubicin (Dox), cetuximab, adenovirus (Ad) and vaccinia virus (VV), representing a scale of sophistication from a simple small-molecule drug to complex biological agents. To achieve tight regulation of the level and duration of cavitation exposure, a “cavitation test rig” was designed and built. The activity of each agent was assessed with and without exposure to a defined cavitation regime which has previously been shown to provide effective and safe delivery of agents to tumors in preclinical studies. The fluorescence profile of Dox remained unchanged after exposure to cavitation, and the efficacy of this drug in killing a cancer cell line remained the same. Similarly, the ability of cetuximab to bind its epidermal growth factor receptor target was not diminished following exposure to cavitation. The encoding of the reporter gene luciferase within the Ad and VV constructs tested here allowed the infectivity of these viruses to be easily quantified. Exposure to cavitation did not impact on the activity of either virus. These data provide compelling evidence that the US parameters used to safely and successfully delivery nanomedicines to tumors in preclinical models do not detrimentally impact on the structure or activity of these nanomedicines. Keywords: nanomedicine, antibody, virus, ultrasound, cavitationMyers RGrundy MRowe CCoviello CMBau LErbs PFoloppe JBalloul JMStory CCoussios CCCarlisle RDove Medical PressarticleNanomedicineantibodyvirusultrasoundcavitationMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 337-349 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nanomedicine antibody virus ultrasound cavitation Medicine (General) R5-920
spellingShingle	Nanomedicine antibody virus ultrasound cavitation Medicine (General) R5-920 Myers R Grundy M Rowe C Coviello CM Bau L Erbs P Foloppe J Balloul JM Story C Coussios CC Carlisle R Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
description	Rachel Myers,1 Megan Grundy,2 Cliff Rowe,1 Christian M Coviello,1 Luca Bau,2 Philippe Erbs,3 Johann Foloppe,3 Jean-Marc Balloul,3 Colin Story,1 Constantin C Coussios,2 Robert Carlisle2 1OxSonics Ltd, The Magdalen Centre, 2BUBBL, IBME, Department of Engineering Science, University of Oxford, Oxford, UK; 3Transgene SA, Illkirch-Graffenstaden, France Abstract: The treatment of cancer using nanomedicines is limited by the poor penetration of these potentially powerful agents into and throughout solid tumors. Externally controlled mechanical stimuli, such as the generation of cavitation-induced microstreaming using ultrasound (US), can provide a means of improving nanomedicine delivery. Notably, it has been demonstrated that by focusing, monitoring and controlling the US exposure, delivery can be achieved without damage to surrounding tissue or vasculature. However, there is a risk that such stimuli may disrupt the structure and thereby diminish the activity of the delivered drugs, especially complex antibody and viral-based nanomedicines. In this study, we characterize the impact of cavitation on four different agents, doxorubicin (Dox), cetuximab, adenovirus (Ad) and vaccinia virus (VV), representing a scale of sophistication from a simple small-molecule drug to complex biological agents. To achieve tight regulation of the level and duration of cavitation exposure, a “cavitation test rig” was designed and built. The activity of each agent was assessed with and without exposure to a defined cavitation regime which has previously been shown to provide effective and safe delivery of agents to tumors in preclinical studies. The fluorescence profile of Dox remained unchanged after exposure to cavitation, and the efficacy of this drug in killing a cancer cell line remained the same. Similarly, the ability of cetuximab to bind its epidermal growth factor receptor target was not diminished following exposure to cavitation. The encoding of the reporter gene luciferase within the Ad and VV constructs tested here allowed the infectivity of these viruses to be easily quantified. Exposure to cavitation did not impact on the activity of either virus. These data provide compelling evidence that the US parameters used to safely and successfully delivery nanomedicines to tumors in preclinical models do not detrimentally impact on the structure or activity of these nanomedicines. Keywords: nanomedicine, antibody, virus, ultrasound, cavitation
format	article
author	Myers R Grundy M Rowe C Coviello CM Bau L Erbs P Foloppe J Balloul JM Story C Coussios CC Carlisle R
author_facet	Myers R Grundy M Rowe C Coviello CM Bau L Erbs P Foloppe J Balloul JM Story C Coussios CC Carlisle R
author_sort	Myers R
title	Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
title_short	Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
title_full	Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
title_fullStr	Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
title_full_unstemmed	Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
title_sort	ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/c577637403ca43e89c1b3be55c5fe0f8
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Ultrasound-mediated cavitation does not decrease the activity of small molecule, antibody or viral-based medicines

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