Multifunctional nanoparticles for image-guided radiotherapy – TheraGuIma

The TheraGuIma project aims at designing multifunctional nanoparticles for image-guided radiotherapy which is expected to significantly improve the brain cancer therapy. There is indeed a real need to propose innovative strategy since the survival of patients suffering from glioblastoma (the most aggressive and the most common brain tumors) does unfortunately not increase despite the tremendous efforts devoted to the improvements of cancer therapy. Although radiotherapy is presented as the most efficient treatment against brain tumors, it suffers from a lack of selectivity in the killing effect leading to numerous adverse effects in normal healthy tissues surrounding the lesion. A better selectivity is therefore required for eradicating the tumor while sparing the surrounding healthy tissues. In addition to the modulation of irradiation parameters, the accumulation of drugs containing heavy elements (high Z) in the tumor has been proposed for improving the selectivity of the radiotherapy since heavy elements generate a dose-enhancement of ionizing radiation (X- or gamma-ray).
TheraGuIma project gathers eight skilled and complementary partners (from university and industry) for improving the selectivity of the radiotherapy. This innovative strategy rests on the development of nanoparticles combining medical imaging and radiosensitizing effect. These multifunctional nanoparticles will be obtained from high Z elements (Gd, Lu and Au). These elements will confer to the nanoparticles the ability to enhance both the dose effect of ionizing radiation applied for radiotherapy (radiosensitization) and the contrast of X-ray images. The composition of the nanoparticles will be tuned in order to follow up the nanoparticles by other medical imaging (magnetic resonance imaging (MRI), Single photon emission computed tomography (SPECT) or positron emission tomography (PET) and eventually fluorescence imaging). Moreover the control of the size (ideally <5 nm) and the chemical composition of the surface will receive a peculiar attention because they exert a preponderant influence on the accumulation in tumor and on the renal clearance. The optimal tumor-to-normal tissue high Z element ratio which must be as high as possible for eradicating the tumor while sparing the healthy tissue requires the functionalization of the nanoparticles by peptides (cRGD, ATWLPPR) for an active targeting of the zone to be treated. The possibility to monitor the biodistribution and the clearance of the nanoparticles by various medical imaging constitutes a great asset because the cytotoxic effect induced by the absorption of the ionizing radiation by the nanoparticles can be initiated at the most opportune moment (i.e. when the ratio is the highest). The potential of the various multifunctional nanoparticles developed in the framework of TheraGuIma for the image-guided radiotherapy will be evaluated by in vitro and in vivo irradiation experiments.