RayPDT — Radiation-powered Photodynamic Therapy
Ionizing radiation-powered PDT for targeted cancer treatment in collaboration with ELI-RO.
Summary
The project focuses on advancing cancer treatment through the innovative approach of Ionizing Radiation-Driven Photodynamic Therapy (IR-PDT). Conventional Photodynamic Therapy (PDT) utilizes light and photosensitizing molecules (PS) to target and destroy cancerous cells. PS was shown to act as a radio-reactive molecule by enhancing generation of reactive oxygen species upon high energy irradiation. This project aims to enhance PDT by utilizing ionizing radiation, for deeper tissue penetration and more effective tumor targeting.
The key innovation lies in developing photosensitizer (PS) functionalized nanostructures that can be activated by the secondary radiation field generated by high-power, short-pulse lasers at ELI-NP facility. These nanostructures are designed to amplify the generation of reactive oxygen species (ROS) when exposed to ionizing radiation, thereby increasing the efficacy of cancer cell destruction. The efficacy of this method will be evaluated through comprehensive in vitro biological assays using three-dimensional cellular models, such as spheroids to closely replicate human cellular responses.
The project adheres to the direction outlined in the ELI-NP White Book, Laser Driven Experiments (LDE) / LDE III Materials in extreme environments / LDE III.6 Biological Systems under Irradiation.
Project Details
Project Team
Stage Reports
Up-date of the project concept and design of the project experiments. Design and photophysical characterization of the PS-nanocompounds (part I). Preliminary biological assays.
The concept model was updated based on project-specific detailed activities and the latest literature reports, involving selection and acquisition of appropriate compounds and equipment, and identification of suitable photosensitizers. Photophysical and spectroscopic characterisation of the compounds (Part I) was performed and protocols for scintillation NP synthesis were developed. The design of the irradiation system and protocol to be followed was established. High-power laser-induced high-energy and high-flux photon beams through the Bremsstrahlung mechanism and dose measurements were performed. A standardised operating procedure for generating viable and reproducible 3D spheroids from human cancer cell lines of different origins was developed. These multicellular tumour spheroids serve as platforms for evaluating PS-nanocompounds in an X-PDT setup. Experimental setup design and standardised protocols for biological testing on normal and tumoral cells were also established.
Design and photophysical characterization of the PS-nanocompounds (part II). Dosimetry of the secondary radiation emitted through laser-target interaction. Testing experiments, optimisation and biological assays.
Scintillation nanoparticles were synthesised and functionalised with several photosensitizers (PS). Photophysical, spectroscopic, and morphological characterisation of the PS-NP complexes was performed by spectroscopic methods (steady-state absorption, excitation and emission fluorescence spectroscopy, time-resolved phosphorescence of generated singlet oxygen), Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and X-ray induced photoemission. Optimised nanocomplexes with efficient singlet oxygen generation were identified. A dosimetric characterisation (spectrum, energy, particle flux) of the secondary radiation emitted following high laser power-target interaction was developed. X-ray-induced PDT was performed on 2D and 3D tumoral and healthy cell lines; optimum radiation dose and PS-NPs complexes were determined. Laser-driven X-ray PDT was compared with conventional X-ray PDT at similar doses.