A Novel Patient-Personalized Nanovector Based on Homotypic Recognition and Magnetic Hyperthermia for an Efficient Treatment of Glioblastoma Multiforme

Glioblastoma multiforme (GBM) is the deadliest brain tumor, characterized by an extreme genotypic and phenotypic variability, besides a high infiltrative property in healthy tissues. Apart from very invasive surgical procedures, to date, there are no effective treatments, and life expectancy is very limited. In this work, we propose an innovative therapeutic approach based on lipid-based magnetic nanovectors, owning a dual therapeutic function: chemotherapy, thanks to an antineoplastic drug (regorafenib) loaded in the core, and localised magnetic hyperthermia, thanks to the presence of iron oxide nanoparticles, remotely activated by an alternating magnetic field. The drug has been selected based on ad hoc patient-specific screenings; moreover, the nanovector is decorated with cell membranes derived from patients' cells, aiming at increasing homotypic and personalized targeting. We demonstrated that this functionalization not only enhances the selectivity of the nanovectors towards patient-derived GBM cells, but also their blood-brain barrier in vitro crossing ability. The localised magnetic hyperthermia induces both thermal and oxidative intracellular stress, that lead to lysosomal membrane permeabilization and release of proteolytic enzymes into the cytosol. Collected results show that hyperthermia and chemotherapy work in synergy to reduce GBM cell invasion properties, to induce intracellular damage and, eventually, to prompt cellular death. This article is protected by copyright. All rights reserved.

glioblastoma; homotypic targeting; magnetic hyperthermia; personalized medicine.