Multifunctional Gold Nanoparticles for Image-Guided Microbeam Radiation Therapy

International audienceOwing to their large range of properties which can be accurately tuned by the chemical composition, the shape and the dimensions, multifunctional nanoparticles appear as promising candidates for imageguided therapy. For achieving this goal, we developed the synthesis of gold nanoparticles which are designed for combining multimodal imaging (magnetic resonance imaging (MRI), scintigraphy (SPECT), ultrasound imaging (echography) and X-ray imaging) and radiotherapy [1-5]. Ultrasmall gold nanoparticles were synthesized by reducing gold salt in presence of various highly hydrophilic dithiolated polyaminocarboxylate ligands (linear (DTDTPA) and macrocyclic (TADOTA, TADOTAGA) ligands). They are composed of a gold core (mean diameter of ~ 2.5 nm) encapsulated within an organic shell of ligands (DTDTPA, TADOTA or TADOTAGA). The gold core is expected to provide a strong X-ray absorption whereas the ligands of the organic shell were chosen for their propensity to entrap gadolinium ions (for MRI) and radionuclides (for SPECT). Since the passive accumulation of the gold nanoparticles in the tumor depends on the nature of theligands, the possibility to follow up the gadolinium chelate-coated gold nanoparticles by MRI is therefore very useful for determining the most opportune delay between intravenous injection and irradiation. Owing to the radiosensitizing effect of the gold core, the combination of microbeamradiation therapy (MRT) and gold nanoparticles based MRI contrast agents led to a great increase in lifespan of the 9L gliosarcoma-bearing rats in comparison to non-treated animals and animals treated only by MRT [5]. Finally, this study demonstrated that gadolinium chelate-coated gold nanoparticles exhibit a real potential for image-guided microbeam radiation therapy