Radiosensitive nanodroplets for theranostic applications in radiotherapy

Radiotherapy is a powerful weapon in the fight against cancer, however, its efficacy is often hindered by tumor radioresistance and the inability to verify treatment delivery, which prevents safe dose escalation. Recently, ultrasound contrast agents were shown to improve the efficacy of radiotherapy treatments through multiple synergistic pathways, from tumor reoxygenation and  cavitation-enhanced radiotherapy to combined targeted drug delivery. In parallel, we showed that liquid nanodroplets can vaporize into echogenic microbubbles when exposed to proton radiation. This behaviour can be directly exploited for ultrasound-based treatment verification, as nanodroplets can act as in situ radiation dose sensors, but can also benefit the aforementioned theranostic applications, as therapeutic effects can be locally triggered by ionizing radiation. However, an important limitation remains to be solved: the nanodroplet response to conventional radiotherapy beams at physiological temperature is currently unexploitable. Therefore, we propose to develop and validate a nanodroplet formulation that is sensitive to radiotherapy photons, thus enabling treatment verification and theranostic applications during the most widely used form of radiotherapy. We will characterize the nanodroplet stability and safety in vitro and in vivo, study their acoustic properties, and demonstrate their sensitivity to photon radiotherapy beams in healthy and tumour bearing animal models.