Orally Administered Oxygen Nanobubbles Enhance Tumour Response to Sonodynamic Therapy

Joshua Owen, Kieran Logan, Heather Nesbitt, Sarah Able, Alexandra Vasilyeva, Emma Bluemke, Veerle Kersemans, Sean Smart, Katherine Vallis, Anthony P. McHale, J Callan, Eleanor Stride

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Suspensions of oxygen-filled bubbles are under active investigation as a potential means of relieving tissue hypoxia. Intravenous administration of large quantities of bubbles is, however, undesirable. Previous work by the authors has demonstrated that tumour oxygen levels can be increased following oral administration of phospholipid stabilised oxygen nanobubbles. The aim of this study was to determine whether this would enhance the efficacy of sonodynamic therapy (SDT), which is known to be inhibited in hypoxic tissue. Experiments were conducted in a murine model of pancreatic cancer. Animals were treated with SDT (intratumoural injection of 1 mM Rose Bengal followed by exposure to 1 MHz ultrasound, 1 kHz pulse repetition frequency, 30% duty cycle, 3.5 W cm-2 for 3.5 minutes) either with or without a prior gavage of oxygen bubbles. A statistically significant reduction in the rate of tumour growth was observed in the groups receiving oxygen nanobubbles either 5 or 20 minutes before SDT. Separate measurements of tumour oxygen using a fibre optic probe and expression of hypoxia inducible factor (HIF)1α following tumour excision, confirmed the change in tumour oxygen levels. These findings offer a potentially promising new approach to relieving tissue hypoxia in order to facilitate cancer therapy.
Original languageEnglish
JournalNano Select
Early online date25 Jun 2021
Publication statusPublished online - 25 Jun 2021


  • nanobubbles
  • hypoxia
  • oxygen delivery
  • sonodynamic therapy
  • ultrasound


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