title: Oxygen carrying microbubbles for enhanced sonodynamic therapy of hypoxic tumours.
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.
authors: Biomedical Sciences Research Institute, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.
authors: Conor
authors: C
authors: McEwan
authors: Oxford Institute of Biomedical Engineering, University of Oxford, Oxford, OX3 7DQ, UK.
authors: Joshua
authors: J
authors: Owen
authors: Oxford Institute of Biomedical Engineering, University of Oxford, Oxford, OX3 7DQ, UK.
authors: Eleanor
authors: E
authors: Stride
authors: Biomedical Sciences Research Institute, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.
authors: Colin
authors: C
authors: Fowley
authors: Biomedical Sciences Research Institute, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.
authors: Heather
authors: H
authors: Nesbitt
authors: Biomedical Sciences Research Institute, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.
authors: David
authors: D
authors: Cochrane
authors: Oxford Institute of Biomedical Engineering, University of Oxford, Oxford, OX3 7DQ, UK.
authors: Constantin C
authors: CC
authors: Coussios
authors: Department of Mechanical Engineering, University of Colorado, 1111 Engineering Drive, Boulder, CO 80309, USA.
authors: M
authors: M
authors: Borden
authors: Division of Surgery & Interventional Science, Medical School, University College London, London W1W 7EJ, UK.
authors: Nikolitsa
authors: N
authors: Nomikou
authors: Biomedical Sciences Research Institute, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK.
authors: Anthony P
authors: AP
authors: McHale
authors: Biomedical Sciences Research Institute, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK. Electronic address: j.callan@ulster.ac.uk.
authors: John F
authors: JF
authors: Callan
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000473:pathology / Q000628:therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D045423:Microbubbles / Q000627:therapeutic use*; D010100:Oxygen / Q000008:administration & dosage / Q000627:therapeutic use*; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000150:complications / Q000473:pathology / Q000628:therapy*; D010778:Photochemotherapy / Q000379:methods; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D012395:Rose Bengal / Q000008:administration & dosage / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D017319:Photosensitizing Agents; D012395:Rose Bengal; D010100:Oxygen
keywords: Cancer; Hypoxia; Microbubbles; Pancreatic; Rose Bengal; SDT