Abstract

AbstractSuspensions of oxygen‐filled bubbles are under active investigation as potential means of relieving tissue hypoxia. Intravenous administration of large quantities of bubbles is, however, undesirable. Previous work by the authors has demonstrated that tumor oxygen levels can be increased following oral administration of phospholipid stabilized 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, 0.1 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 tumor growth was observed in the groups receiving oxygen nanobubbles either 5 or 20 minutes before SDT. Separate measurements of tumor oxygen using a fiber optic probe and expression of hypoxia inducible factor (HIF)1α following tumor excision, confirmed the change in tumor oxygen levels. These findings offer a potentially promising new approach to relieving tissue hypoxia in order to facilitate cancer therapy.

Highlights

  • Hypoxia, that is, an imbalance between oxygen supply and consumption, is a common feature of solid tumors

  • A statistically significant difference in the rate of change tumor volume was observed between the groups receiving sonodynamic therapy (SDT) only and those receiving both SDT and oxygen bubbles 19 days after treatment (Figure 3)

  • The results of this study showed that an improved response to SDT was observed following oral administration of oxygen nanobubbles in a mouse model of pancreatic cancer

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Summary

Introduction

That is, an imbalance between oxygen supply and consumption, is a common feature of solid tumors. Tumor hypoxia is associated with impaired therapeutic response, malignant progression and poor clinical outcomes.[3,4] In particular it has been shown to lower the efficacy of treatments dependent on reactive oxygen species (ROS) generation, such as chemo-, radio- and photodynamic therapy.[5,6] This is

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