Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles as a delivery vehicle

Conor McEwan, Sukanta Kamila, Joshua Owen, Heather Nesbitt, Bridgeen Callan, Mark Borden, Nikolitsa Nomikou, Rifat A Hamoudi, Mark A Taylor, Eleanor Stride, AP McHale, J Callan

Research output: Contribution to journalArticle

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Abstract

In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. 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 with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was 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 to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the potential of combined SDT/antimetabolite therapy as a stand alone treatment option in pancreatic cancer, but also the capability of O2-loaded MBs to deliver O2 to the tumour microenvironment in order to enhance the efficacy of therapies that depend on O2 to mediate their therapeutic effect. Furthermore, the use of MBs to facilitate delivery of O2 as well as the sensitiser/antimetabolite, combined with the possibility to activate the sensitiser using externally applied ultrasound, provides a more targeted approach with improved efficacy and reduced side effects when compared with conventional systemic administration of antimetabolite drugs alone.
LanguageEnglish
Pages20-32
Number of pages13
JournalBiomaterials
Volume80
Early online date25 Nov 2015
DOIs
Publication statusPublished - 29 Feb 2016

Fingerprint

Antimetabolites
Microbubbles
Pancreatic Neoplasms
Tumors
Oxygen
Cells
Fluorouracil
Therapeutics
Ultrasonics
Rose Bengal
Heterografts
Tumor Microenvironment
SCID Mice
Therapeutic Uses
Neoplasms
Cell Survival
Pharmaceutical Preparations

Keywords

  • Hypoxia
  • Microbubbles
  • SDT
  • Rose Bengal
  • 5-Flurouracil
  • Cancer
  • Pancreatic

Cite this

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title = "Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles as a delivery vehicle",
abstract = "In this manuscript we describe the preparation of an oxygen-loaded microbubble (O2MB) platform for the targeted treatment of pancreatic cancer using both sonodynamic therapy (SDT) and antimetabolite therapy. 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 with respect to size, physical stability and oxygen retention. A statistically significant reduction in cell viability was 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 to either therapy alone. In addition, a statistically significant reduction in tumour growth was also observed when ectopic human xenograft BxPC-3 tumours in SCID mice were treated with the combined therapy compared to treatment with either therapy alone. These results illustrate not only the potential of combined SDT/antimetabolite therapy as a stand alone treatment option in pancreatic cancer, but also the capability of O2-loaded MBs to deliver O2 to the tumour microenvironment in order to enhance the efficacy of therapies that depend on O2 to mediate their therapeutic effect. Furthermore, the use of MBs to facilitate delivery of O2 as well as the sensitiser/antimetabolite, combined with the possibility to activate the sensitiser using externally applied ultrasound, provides a more targeted approach with improved efficacy and reduced side effects when compared with conventional systemic administration of antimetabolite drugs alone.",
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Combined sonodynamic and antimetabolite therapy for the improved treatment of pancreatic cancer using oxygen loaded microbubbles as a delivery 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; Callan, J.

In: Biomaterials, Vol. 80, 29.02.2016, p. 20-32.

Research output: Contribution to journalArticle

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AU - McEwan, Conor

AU - Kamila, Sukanta

AU - Owen, Joshua

AU - Nesbitt, Heather

AU - Callan, Bridgeen

AU - Borden, Mark

AU - Nomikou, Nikolitsa

AU - Hamoudi, Rifat A

AU - Taylor, Mark A

AU - Stride, Eleanor

AU - McHale, AP

AU - Callan, J

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KW - Rose Bengal

KW - 5-Flurouracil

KW - Cancer

KW - Pancreatic

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