Ionizing radiation-powered photodynamic therapy for targeted cancer treatment
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. Through this project, we seek to advance the understanding and application of ionizing radiation-driven PDT on deep malignant tumors.
To fulfils the project goal, specific objectives must be achieved: *selection of proper photosensitizers to be used in nanostructures design; *synthesis and characterization of nanoparticles, encompassing morphological and structural analyses; * attainment and characterization (spectroscopic, photophysical, microfluidic, morphological) of the PS functionalized nanoparticles; * Evaluation of ROS species generation efficiency by PS-Np upon activation by light/X-ray.* Investigation of interaction with targeted cancer receptors through computational binding interaction and determination of energies via docking simulations; *measurements of the X ray and γ-rays doses emitted by different experimental set-ups developed at ELI-NP (different type of targets); * Ionizing Radiation-PDT tests, asses the antitumoral efficiency of PS-NPs by several biological 3D assays.
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.
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