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Description
Cancer remains one of the most important global health challenges of the 21st century and one of the leading causes of death worldwide. Radiotherapy is a cornerstone of modern cancer oncology, with more than half of all cancer patients receiving curative or palliative radiotherapy as part of their treatment. However, even with continual technological improvements, radiotherapy can be limited by toxicity to surrounding healthy tissues, resistance mechanisms, and unfavourable tumour locations. These limitations highlight the need for complementary modalities capable of enhancing tumour control while reducing treatment-related side effects.
Photodynamic therapy (PDT) is an emerging clinically approved modality that offers high specificity, low invasiveness, and reduced side effects. Under light activation, photosensitizers generate reactive oxygen species (ROS) that induce cytotoxic effects in tumour cells. Nevertheless, conventional PDT suffers from shallow penetration depth due to the strong absorption and scattering of UV-visible light in biological tissues, restricting its application to superficial lesions.
To overcome this fundamental limitation, X-ray induced photodynamic therapy (X-PDT) has been proposed, exploiting the deep penetration capability of X-rays. In this study, we present an in vitro assessment of nanoparticle-mediated X-PDT using a high-power laser-driven source. Cerium-doped titanium dioxide (Ce:TiO₂) nanoparticles were synthesized via a sol-gel method and conjugated with a porphyrin-based photosensitizer (TMPyP4), forming a nanoscintillator-photosensitizer nanocomplex. Spectroscopic characterization confirmed successful photosensitizer loading and efficient energy transfer.
Biological experiments were performed on breast cancer (MDA-MB-231) and normal epithelial (MCF-12A) cell lines irradiated at the ELI-NP E6 experimental area using a broadband laser-driven Bremsstrahlung X-ray source. Dose rates exceeding 10¹¹ Gy/s were achieved, far above the FLASH radiotherapy threshold. Clonogenic survival, MTT, and comet assays revealed significant DNA damage and cytotoxic effects in cancer cells. These results demonstrate the feasibility and therapeutic potential of laser-driven X-PDT for deep-seated tumour treatment.