BJS 2 - Tumour targeted oxygen-generating nanoparticles for enhanced radiotherapy in the treatment of pancreatic cancer

Sian Farrell, Thomas McKaig, Tierna Gillan, Heather Nesbitt, Mark Talyor, John Callan, Anthony McHale

Research output: Contribution to journalArticlepeer-review

Abstract

Aim
To determine if novel oxygen-generating nanoparticles, encased in a pH-sensitive polymethacrylate polymer (SOG-01), can enhance radiotherapy-based treatment in a preclinical pancreatic cancer model. SOG-01 nanoparticles are stable in circulation and, at the lower pH in hypoxic tumours, the polymer coating dissolves to expose a solid peroxide core, capable of generating oxygen in the tumour microenvironment. Since hypoxia reduces the efficacy of radiotherapy, this particle could potentially be employed to enhance radiotherapy-based approaches for the treatment of pancreatic cancer.

Methods
A human xenograft pancreatic cancer model (BxPC-3) in mice was employed as a target. SOG-01 was administered systemically and animals (n=6 per experimental group) were subsequently treated with radiation (a single dose of 6 Gy) using a Gulmay (160kV) AGO HS-MP1 X-Ray generator. Control animals were either untreated, treated with SOG-01 alone, or radiation alone. Tumour size and survival were employed as a measure of therapeutic efficacy.

Results
When the mean tumour size of groups treated with SOG-01 or radiation alone was compared with that of the untreated group at day 23 no statistically significant decrease was observed. However, a dramatic 89% and statistically significant decrease (p = 0.001; α = 0.05) was observed for tumours treated with combination of SOG-01 and radiation. Additionally, Kaplan Meier analysis demonstrated enhanced survival to 65 days when compared with 38 day survival for the group treated with radiation alone.

Conclusions
The data suggest that SOG-01 may play a role in enhancing radiotherapy-based approaches for the treatment of pancreatic cancer.
Original languageEnglish
JournalBritish Journal of Surgery
Volume111
Issue numberSupplement 8
DOIs
Publication statusPublished (in print/issue) - 9 Sept 2024

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