Gold Radiosensitizers for Advanced Proton therapy

Objective

Cancer research efforts nowadays are focused on improving patients’ quality of life through targeted therapies, that decrease adverse effects while improving survival. GRAPE will contribute to this aim by developing therapeutic agents based on biocompatible gold-based nanoparticles (NPs), which will predictably improve proton beam therapy (PBT) outcomes. This will be achieved by not only enhancing the effect of PBT, but also minimizing the off-targeted toxicity that induces damaging of healthy tissues located at the tumor periphery, leading to lower adverse effects related to radiotherapy lack of specificity. The use of therapeutic nanoplatforms could also be used as a starting point for personalized medicine. The physico-chemical properties of the NPs can be rationally designed according to different needs. Additionally, NPs will be functionalized with active targeting in order to enable selective delivery and accumulation inside glioblastoma multiforme (GBM) cancer cells overexpressing certain markers. After testing NPs selective uptake and toxicity in GBM cells, they will be administered in vivo to assess NP retention by tumor tissue. Then, their therapeutic potential will be assessed in vitro employing a clinical proton therapy equipment. Finally, we will preliminary test their therapeutic effect in vivo, employing oncologic mice models with the same clinical equipment. Not only GRAPE aims to provide a more personalized therapy for GBM patients, but also for other cancer types. Once the NPs are validated in GBM, their versatility and adaptability will allow the anchoring of other targeting ligands for surface markers specifically overexpressed by other cancer cells, thus expanding overall oncology treatment options.