Cell membrane-coated magnetic nanocubes with a homotypic targetingability increase intracellular temperature due to ROS scavenging and act as aversatile theranostic system for glioblastoma multiforme

摘要

In this study, we synthesized hybrid nanocubes composed of magnetite (Fe3O4) and manganese dioxide (MnO2), coated with U-251 MG cell-derived membranes (CM-NCubes). The CM-NCubes demonstrated a concentration-dependent oxygen generation (up to 15%), and, for the first time in literature, we showed an intracellular increase of temperature (6°C) due to the exothermic scavenging reaction of hydrogen peroxide (H2O2). Internalization studies demonstrated that the CM-NCubes were internalized much faster and at a higher extent by the homotypic U-251 MG cell line compared to other cerebral cell lines. The ability of the CM-NCubes to cross an in vitro model of the blood-brain barrier (BBB) was also assessed. The CM-NCubes showed the ability to respond to a static magnet and to accumulate in cells even under flowing conditions. Moreover, we demonstrated that 500 μg ml^-1 of sorafenib-loaded and unloaded CM-NCubes are able to induce cell death by apoptosis in U-251 MG spheroids that were used as a tumor model, after their exposure to an alternating magnetic field (AMF). Finally, it was shown that the combination of sorafenib and AMF induces a higher enzymatic activity of caspase 3 and caspase 9, probably due to an increment inreactive oxygen species (ROS) by means of hyperthermia.