Development of a Multi-functional Nanoparticle Platform for Disease Detection, Diagnosis, and Targeted Therapy

Abstract

Molecular imaging and nanotechnology offer new opportunities for medicine, with great promise for improving disease detection, diagnosis and treatment. Applications include enhanced imaging contrast, advanced drug delivery, and more effective radiation therapies, often combined into a theranostic (therapeutic and diagnostic) agent. However, the vast array of nanomaterials and their complex biological interactions present scientific complexities hindering the translation of nanotheranostics into clinical reality. This thesis explores three commercial nanoparticle platforms: two superparamagnetic iron oxide nanoparticles (SPIONs), PrecisionMRX and Feraheme, and the gadolinium-based nanoparticle AGuIX. Feraheme and AGuIX are computationally evaluated for enhancing radiotherapeutic effects in internal and external beam therapies, respectively, extending their function beyond MRI contrast agents. PrecisionMRX’s performance as an MRI contrast agent is assessed at conventional and ultra-low fields (ULF), in addition to its in vivo biodistribution and clearance. Geant4-based Monte Carlo simulations showed that clustered Feraheme SPIONs significantly amplify secondary electron production when radiolabelled with copper-67, demonstrating that the specific spatial configuration of nanoparticles has a large impact on the degree of radio-enhancement provided. AGuIX also produced substantial radio-enhancement from its unique geometry, particularly when clustered or doped with bismuth. In vivo, PrecisionMRX SPIONs showed rapid uptake in the liver, spleen and renal system, providing effective conventional MRI contrast in addition to a novel bright contrast enhancement based on susceptibility gradient mapping (SGM). It also generated strong positive contrast in ultra-low field MRI, outperforming conventional agents. These findings show the potential of these nanoplatforms to enhance advanced medical imaging and augment advanced techniques in radiation therapy.