Enhancing cancer radiotherapy efficacy using NanOx, a novel oxygenating perfluorocarbon nanoemulsion that reverses tumour hypoxia

Abstract

Radiotherapy is used to treat over 50 % of cancer patients. It is often used in combination with surgery, chemotherapy, and immunotherapy, for cancers of the breast, lung, oesophagus, and rectum. Ionising radiation predominantly exerts its anti-cancer effect through both direct DNA damage and indirectly via water radiolysis and the production of reactive oxygen species. This DNA damage is made permanent in the presence of molecular oxygen; however, it is reversible under hypoxia. Therefore, hypoxia confers significant radiotherapy resistance and given that it is a common feature of most solid tumours it offers a unique tumour vulnerability to exploit to improve radiotherapy efficacy. Many efforts to increase radiotherapy efficacy by oxygen delivery have failed due to limited efficacy and toxicity. To address this, we have developed a biocompatible, oxygenating perfluorocarbon nanoemulsion (nPFC) with imaging capacity via microCT with the view of delivering this intratumourally. We have demonstrated that this nPFC is biocompatible using an in vitro 3D liver hepatotoxicity model and in vivo using a developmental zebrafish embryo model. We have also shown that our nPFC can load and deliver a significant amount of molecular oxygen, reverse hypoxia, and enhance cellular radiosensitivity in an established in vitro isogenic model of acquired radioresistance in oesophageal adenocarcinoma (OAC) in accordance with the oxygen enhancement effect. Overall, this study demonstrates a potential method of enhancing cancer radiotherapy efficacy by locoregional oxygen delivery to hypoxic cells with acquired radioresistance.