GLADIATOR · Next-generation theranostics of brain pathologies with autonomous externally controllable nanonetworks: a trans-disciplinary approach with bio-nanodevice interfaces

Brain pathologies are highly complex disorders. Despite recent progress, their prognosis is grim, defining a high societal challenge. Bridging life sciences, bio-nanotechnology, engineering and ICT, GLADIATOR promises a vanguard and comprehensive theranostic (therapeutic+diagnostic) solution for brain malignancies. Through a multi-faceted breakthrough, GLADIATOR will provide, for the first time, a working prototype of a complete, autonomous and clinically applicable, nanonetwork-based, Molecular Communications system based on the conceptual framework of Externally Controllable Molecular Communications (ECMC). Using Glioblastoma Multiforme tumours, the most detrimental brain pathologies, as a proof-of-concept case, GLADIATOR will implement a platform of cell-based and electronic components. Implantable autologous organoids of engineered neural stem cells (iNSCs) will release rationally designed exosomal bio-nanomachines, delivering reprogramming (therapeutic) miRNAs and building nanonetworks. Interfering with the underlying biological environment, the nanonetworks will define a revolutionary intervention. A hybrid bio-electronic interface, consisting of coupled external and implantable devices, will enable communication channels with host-derived fluorescent bio-nanomachines via micro-optoelectronic sensors. The cellular, sub-cellular and electronic components will be integrated into a wireless ECMC network. This system will autonomously monitor the spatiotemporal tumour evolution and recurrence and generate, on demand, appropriate reprogramming interventions, by radiofrequency stimulation of iNSC renewal. A paradigm shift in Oncology Research is anticipated via the supra-discipline of “bio-nanomachine diagnostics”. GLADIATOR establishes a radical long-term vision leading to a drastic change in cancer therapy, also ushering the emergence of the ECMC field and transforming the burgeoning industry of Internet of Nano-bio-things, with high socioeconomic impact.