Smart drug delivery systems (SDDS) represent an innovative way to treat glioblastoma multiforme (GBM) by holding attractive characteristics like biomimicry, easiness in crossing the blood brain barrier (BBB) and multi-stimuli responsiveness, that enhance the therapeutic effectiveness and reduce the side-effects of the current treatment strategies. In this study, we hypothesized that the coating, with a GBM cell membrane, of a composite nanoparticle (NP) consisting of a magnetic core and an antioxidant shell (MANP), and its loading with the drug temozolomide (TMZ), could represent a novel system with an inherent targeting ability that can effectively treat GBM. These MANPs have also the potential to be used for guided delivery and as magnetic resonance imaging contrast agents.