Glioblastoma, the most aggressive brain cancer, has a low median survival after surgery or chemotherapy. Even immunotherapy, considered a promising strategy to delay the progression of glioblastoma has not provided the expected results. The microenvironment generated by glioblastoma is per se immunosuppressive and its heterogeneity is the main cause of chemoresistance. The advent of theranostic nanomedicine, a combination of imaging and therapeutic agents, represents new road for malignant brain tumors eradication. The possibility to synergistically combine cancer therapy and detection by exploiting radio labeled biomimetic gold nanoparticles (Au NPs) with tailored thermo-optical properties, represents a new horizon in the field of drug-free cancer therapy. This goal is accomplished through the conjugation of biomimetic protein capped (Keratin) Au NPs (Ker-AuNPs) with a sugar-based radio tracer (fluorodeoxyglucose,18F-FDG). The FDG-Ker-AuNPs is used as a Trojan horse for targeting (FDG accumulates in energy-hungry cancer cells), detecting (18Fpositron emission isotope) and burning (Ker-AuNPs photo-thermal properties) glioblastoma tumour cells. Here, we propose an innovative approach based on the combination of targeting, detection, and therapy, by verifying the therapeutical biological effects of FDG-Ker-AuNPs in a 3D bioprinted model of human primary glioblastoma. Thus, FDG-Ker-AuNPs will selectively recognize the glioblastoma cells assembled in a 3D model and the 18F will detect and localize in the construct with very high precision NPs by computer and positron emission tomography technology. This strategy will allow us to investigate the physiological spatial and heterogenous distribution of glioblastoma testing the efficacy/toxicity of the drug delivered by FDG-Ker-AuNPs. The end-goal is to perform an in vitro-in vivo correlation unlocking the possibility to realize innovative studies based on an animal free glioblastoma cancer model.
