Gemcitabine loaded Microbubbles for Targeted Chemo-Sonodynamic Therapy of Pancreatic Cancer

Heather Nesbitt, Yinjie Sheng, Sukanta Kamila, Keiran Logan, Keith Thomas, Bridgeen Callan, Mark Taylor, Mark Love, Paul Kelly, Estelle Beguin, Eleanor Stride, AP McHale, John Callan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Pancreatic cancer remains one of the most lethal forms of cancer with a 10-year survival of <1%. With little improvement in survival rates observed in the past 40 years, there is a significant need for new treatments or more effective strategies to deliver existing treatments. The antimetabolite gemcitabine (Gem) is the most widely used form of chemotherapy for pancreatic cancer treatment, but is known to produce significant side effects when administered systemically. We have previously demonstrated the benefit of combined chemo-sonodynamic therapy (SDT), delivered using oxygen carrying microbubbles (O2MB), as a targeted treatment for pancreatic cancer in a murine model of the disease. In this manuscript, we report the preparation of a biotin functionalised Gem ligand for attachment to O2MBs (O2MB-Gem). We demonstrate the effectiveness of chemo-sonodynamic therapy following ultrasound-targeted-microbubble-destruction (UTMD) of the O2MB-Gem and a Rose Bengal loaded O2MB (O2MB-RB) as a targeted treatment for pancreatic cancer. Specifically, UTMD using the O2MB-Gem and O2MB-RB conjugates reduced the viability of MIA PaCa-2, PANC-1, BxPC3 and T110299 pancreatic cancer cells by greater than 60% (p80%, p
LanguageEnglish
Pages8-16
JournalJournal of Controlled Release
Volume279
Early online date11 Apr 2018
DOIs
Publication statusE-pub ahead of print - 11 Apr 2018

Fingerprint

gemcitabine
Microbubbles
Pancreatic Neoplasms
Therapeutics
Rose Bengal
Antimetabolites
Biotin

Keywords

  • Pancreatic cancer
  • microbubbles
  • gemcitabine
  • ultrasound
  • sonodynamic therapy
  • antimetabolite therapy.

Cite this

Nesbitt, Heather ; Sheng, Yinjie ; Kamila, Sukanta ; Logan, Keiran ; Thomas, Keith ; Callan, Bridgeen ; Taylor, Mark ; Love, Mark ; Kelly, Paul ; Beguin, Estelle ; Stride, Eleanor ; McHale, AP ; Callan, John. / Gemcitabine loaded Microbubbles for Targeted Chemo-Sonodynamic Therapy of Pancreatic Cancer. In: Journal of Controlled Release. 2018 ; Vol. 279. pp. 8-16.
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Gemcitabine loaded Microbubbles for Targeted Chemo-Sonodynamic Therapy of Pancreatic Cancer. / Nesbitt, Heather; Sheng, Yinjie; Kamila, Sukanta; Logan, Keiran; Thomas, Keith; Callan, Bridgeen; Taylor, Mark; Love, Mark; Kelly, Paul; Beguin, Estelle; Stride, Eleanor; McHale, AP; Callan, John.

In: Journal of Controlled Release, Vol. 279, 11.04.2018, p. 8-16.

Research output: Contribution to journalArticle

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AU - Thomas, Keith

AU - Callan, Bridgeen

AU - Taylor, Mark

AU - Love, Mark

AU - Kelly, Paul

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AU - Stride, Eleanor

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AU - Callan, John

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