Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours

C McEwan, J Owen, E Stride, Colin Fowley, Heather Nesbitt, D Cochrane, M Borden, CC Coussios, N Nomikou, AP McHale, J Callan

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

Tumour hypoxia represents a major challenge in the effective treatment of solid cancerous tumours using conventional approaches. As oxygen is a key substrate for Photo-/Sono-dynamic Therapy (PDT/SDT), hypoxia is also problematic for the treatment of solid tumours using these techniques. The ability to deliver oxygen to the vicinity of the tumour increases its local partial pressure improving the possibility of ROS generation in PDT/SDT. In this manuscript, we investigate the use of oxygen-loaded, lipid-stabilised microbubbles (MBs), decorated with a Rose Bengal sensitiser, for SDT-based treatment of a pancreatic cancer model (BxPc-3) in vitro and in vivo. We directly compare the effectiveness of the oxygen-loaded MBs with sulphur hexafluoride (SF6)-loaded MBs and reveal a significant improvement in therapeutic efficacy. The combination of oxygen-carrying, ultrasound-responsive MBs, with an ultrasound-responsive therapeutic sensitiser, offers the possibility of delivering and activating the MB-sensitiser conjugate at the tumour site in a non-invasive manner, providing enhanced sonodynamic activation at that site.
Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalJournal of Controlled Release
Volume203
Early online date4 Feb 2015
DOIs
Publication statusPublished - 10 Apr 2015

Keywords

  • Hypoxia
  • Microbubbles
  • SDT
  • Rose Bengal
  • Cancer
  • Pancreatic

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