Magnetic Microbubble Mediated Chemo-Sonodynamic Therapy using a Combined Magnetic-Acoustic Device

Estelle Beguin, Michael D Gray, Keiran Logan, Heather Nesbitt, Yingjie Sheng, Sukanta Kamila, Lester C Barnsley, Luca Bau, Anthony P. McHale, J Callan, Eleanor Stride

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40 Citations (Scopus)
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Abstract

Recent pre-clinical studies have demonstrated the potential of combining chemotherapy and sonodynamic therapy for the treatment of pancreatic cancer. Oxygen-loaded magnetic microbubbles have been explored as a targeted delivery vehicle for this application. Despite preliminary positive results, a previous study identified a significant practical challenge regarding the co-alignment of the magnetic and ultrasound fields. The aim of this study was to determine whether this challenge could be addressed through the use of a magnetic-acoustic device (MAD) combining a magnetic array and ultrasound transducer in a single unit, to simultaneously concentrate and activate the microbubbles at the target site. in vitro experiments were performed in tissue phantoms and followed by in vivo treatment of xenograft pancreatic cancer (BxPC-3) tumours in a murine model. In vitro, a 1.4-fold (p < .01) increase in the deposition of a model therapeutic payload within the phantom was achieved using the MAD compared to separate magnetic and ultrasound devices. In vivo, tumours treated with the MAD had a 9% smaller mean volume 8 days after treatment, while tumours treated with separate devices or microbubbles alone were respectively 45% and 112% larger. This substantial and sustained decrease in tumour volume suggests that the proposed drug delivery approach has the potential to be an effective neoadjuvant therapy for pancreatic cancer patients.

Original languageEnglish
Pages (from-to)23-33
Number of pages11
JournalJournal of Controlled Release
Volume317
Early online date13 Nov 2019
DOIs
Publication statusPublished (in print/issue) - 10 Jan 2020

Bibliographical note

Funding Information:
Funding for the work was provided by the Engineering and Physical Sciences Research Council ( EP/I021795/1 and EP/L024012/1 ) and the Institute of Engineering and Technology (AF Harvey Prize). EB thanks the Research Councils UK Digital Economy Programme for the support through grant EP/G036861/1 ( Oxford Centre for Doctoral Training in Healthcare Innovation ). MDG was supported by the National Institute of Health Research , Oxford Biomedical Research Centre . JFC thanks Norbrook Laboratories Ltd. for an endowed chair. KAL thanks the Department for the Economy in Northern Ireland for a PhD studentship. YS and SK thank Invest N.I. in Northern Ireland and the Pancreatic Cancer Research Fund respectively for postdoctoral fellowships.

Publisher Copyright:
© 2019 The Authors

Keywords

  • Drug delivery
  • Magnetic targeting
  • Medical devices
  • Microbubbles
  • Sonodynamic therapy
  • Ultrasound

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