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

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.