ReachGLIO aims to improve glioblastoma therapy by combining blood–brain barrier opening strategies with targeted, drug-loaded nanoparticles. The project evaluates SNGR‑TNF (a stable derivative of NGR‑TNF) alongside standard chemotherapy and selects nanomedicines designed to penetrate the tumour and reach cancer stem cells. Candidate formulations are tested in advanced BBB/BTB models and 3D glioblastoma models, and then validated in mouse models and in spontaneous gliomas in dogs. Raman spectroscopy-based imaging makes it possible to track drug distribution and release, generating preclinical evidence to accelerate clinical translation.