Radioluminescent nanoparticles and deep-tissue photodynamic therapy to enhance radiotherapy efficacy

Photodynamic therapy (PDT) is an anticancer therapy that relies on the light activation of non-toxic photosensitizers to generate reactive oxygen species (ROS) to damage tumor cells. As the excitation light for PDT lies in the visible range, it can only penetrate up to a few mm in tissues. Therefore, the application of PDT is limited to superficial or optic-fiber accessible tumors. In order to overcome this major limitation, it has been proposed to leverage the particular properties of scintillating nanoparticles, which down-convert ionizing radiation into visible light. Scintillating nanoparticles can therefore act as internal light sources remotely activated by the penetrating X-rays used in radiotherapy to activate deep tissue PDT1, or X-ray induced PDT (XPDT). Proof-of-concept studies have been published, yet the therapeutic mechanisms remain to be fully understood. When using nanoscintillators in combination with radiotherapy, mechanisms other than PDT can also be activated. For example, as nanoscintillators are typically made of high-Z elements, we hypothesized the existence of the purely physical radiation dose-enhancement effect. This effect is initiated by a higher photoelectric absorption of orthovoltage X-rays (< 250 keV) by high-Z elements compared to soft tissues, which leads to a higher production of photo- and Auger electrons that enhance the damage to cancer tissues for a given dose of radiotherapy2. In this communication, we will present the results we recently obtained with Lu3Al5O12:Pr nanoscintillators conjugated to the photosensitizer protoporphyrin IX. More specifically, we will present the ability of these nanoconjugates to enhance the efficacy of radiotherapy through different mechanisms, such as radiation dose enhancement and XPDT, against pancreatic cancer cells cultured both as 2D monolayers and 3D spheroids.