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Combined sonodynamic and antimetabolite therapy for the improvedtreatment of pancreatic cancer using oxygen loaded microbubbles as adelivery vehicle

McEwan, Conor, Kamila, Sukanta, Owen, Joshua, Nesbitt, Heather, Callan, Bridgeen, Borden, Mark, Nomikou, Nikolitsa, Hamoudi, Rifat A, Taylor, Mark A, Stride, Eleanor, McHale, AP and Callan, J (2015) Combined sonodynamic and antimetabolite therapy for the improvedtreatment of pancreatic cancer using oxygen loaded microbubbles as adelivery vehicle. Biomaterials, 80 . pp. 20-32. [Journal article]

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URL: http://www.journals.elsevier.com/biomaterials

DOI: http://dx.doi.org/10.1016/j.biomaterials.2015.11.033


In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform forthe targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolitetherapy. O2MB were prepared with either the sensitiser Rose Bengal (O2MB-RB) or the antimetabolite 5-fluorouracil (O2MB-5FU) attached to the microbubble (MB) surface. The MB were characterised withrespect to size, physical stability and oxygen retention. A statistically significant reduction in cell viabilitywas observed when three different pancreatic cancer cell lines (BxPc-3, MIA PaCa-2 and PANC-1),cultured in an anaerobic cabinet, were treated with both SDT and antimetabolite therapy compared toeither therapy alone. In addition, a statistically significant reduction in tumour growth was also observedwhen ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapycompared to treatment with either therapy alone. These results illustrate not only the potential ofcombined SDT/antimetabolite therapy as a stand alone treatment option in pancreatic cancer, but alsothe capability of O2-loaded MBs to deliver O2 to the tumour microenvironment in order to enhance theefficacy of therapies that depend on O2 to mediate their therapeutic effect. Furthermore, the use of MBsto facilitate delivery of O2 as well as the sensitiser/antimetabolite, combined with the possibility toactivate the sensitiser using externally applied ultrasound, provides a more targeted approach withimproved efficacy and reduced side effects when compared with conventional systemic administrationof antimetabolite drugs alone.

Item Type:Journal article
Keywords:Hypoxia, Microbubbles, SDT, Rose Bengal, 5-Flurouracil,Cancer, Pancreatic
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute > Genomic Medicine
Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Pharmacy & Pharmaceutical Sciences
ID Code:34729
Deposited By: Professor Anthony McHale
Deposited On:08 Jun 2016 09:09
Last Modified:17 Oct 2017 16:23

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