Ultrasound targeted microbubble destruction using docetaxel and Rose Bengal loaded Microbubbles for targeted Chemo-Sonodynamic therapy treatment of prostate cancer

Thomas McKaig, Keiran Logan, Heather Nesbitt, Bridgeen Callan, Stephanie McKeown, Joe M O'Sullivan, Paul Kelly, Declan O'Rourke, Anthony P McHale, John F Callan

Research output: Contribution to journalArticlepeer-review

Abstract

Docetaxel (DTX) chemotherapy is commonly used in the treatment of patients with advanced prostate cancer demonstrating modest improvements in survival. As these patients are often elderly and the chemotherapy treatment is not targeted, it is often poorly tolerated. More targeted approaches that increase therapeutic efficacy yet reduce the amount of toxic chemotherapy administered are needed. In this manuscript, we investigate the potential of ultrasound targeted microbubble destruction (UTMD) to deliver a combination of docetaxel chemotherapy and Rose Bengal mediated sonodynamic therapy (SDT) in pre-clinical prostate cancer models. A Rose Bengal modified phospholipid was synthesized and used as a component lipid to prepare a microbubble (MB) formulation that was also loaded with DTX. The DTX-MB-RB formulation was used in the UTMD mediated treatment of androgen sensitive and androgen resistant 3D spheroid and murine models of prostate cancer. Results from the 3D spheroid experiments showed UTMD mediated DTX-MB-RB chemo-sonodynamic therapy to be significantly more effective at reducing cell viability than UTMD mediated DTX or SDT treatment alone. In an androgen sensitive murine model of prostate cancer, UTMD mediated DTX-MB-RB chemo-sonodynamic therapy was as effective as androgen deprivation therapy (ADT) at controlling tumour growth. However, when both treatments were combined, a significant improvement in tumour growth delay was observed. In an androgen resistant murine model, UTMD mediated DTX-MB-RB chemo-sonodynamic therapy was significantly more effective than standard DTX monotherapy. Indeed, the DTX dose administered using the DTX-MB-RB formulation was 91% less than standard DTX monotherapy. As a result, UTMD mediated DTX-MB-RB treatment was well tolerated while animals treated with DTX monotherapy displayed significant weight loss which was attributed to acute toxic effects. These results highlight the potential of UTMD mediated DTX-MB-RB chemo-sonodynamic therapy as a targeted, well tolerated alternative treatment for advanced prostate cancer.
Original languageEnglish
Pages (from-to)196-205
Number of pages10
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume192
Early online date18 Oct 2023
DOIs
Publication statusPublished (in print/issue) - 30 Nov 2023

Bibliographical note

Funding Information:
The authors acknowledge Prostate Cancer UK for a research innovation award (RIA18-ST2-003). TMcK acknowledges the Department for the Economy in Northern Ireland for a PhD studentship.



Publisher Copyright:
© 2023

Keywords

  • Prostate cancer
  • Androgen deprivation therapy
  • Docetaxel
  • Microbubble
  • Sonodynamic therapy
  • Chemotherapy

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