Glioma stem cell membrane-camouflaged photothermal nanozyme for synergistic antitumor via dual-targeted drug delivery across blood-brain barrier

Abstract

The schematic diagram illustrates the synthesis pathway of the biomimetic nanoenzyme (D@FNMG) and the mechanism of killing glioma cells through combination therapy. • A photothermal nanozyme camouflaged by glioma stem cell membrane was constructed. • Targeted drug delivery across the BBB to both GBM cells and GSC was achieved. • The chemotherapy-CDT-PTT combined therapy promoted tumor apoptosis and ferroptosis. • Demonstrated significant tumor inhibition and survival extension with good biosafety. Glioma stem cells (GSC) are key contributors to the high resistance and recurrence of glioblastoma multiforme (GBM), while the blood–brain barrier (BBB) hinders drug delivery to GBM. In response to these challenges, we have developed a photothermal nanozyme drug delivery system camouflaged with glioma stem cell membrane (GSCM) to synergistically combat GBM. This system employs iron–nitrogen-doped mesoporous carbon nanospheres (FNM) as carriers for doxorubicin (DOX), encapsulated within GSCM. This nanomaterial utilizes GSCM to cross the BBB, target both GSC and GBM cells release DOX under the acidic conditions of the tumor microenvironment (TME) to facilitate chemotherapy. Notably, the system’s inherent peroxidase-like activity catalyzes the conversion of H 2 O 2 into reactive oxygen species (ROS), boosting the level of oxidative stress and promoting tumor cell apoptosis and ferroptosis, thereby synergistically achieving chemodynamic therapy (CDT). Moreover, under near-infrared (NIR) irradiation, the photothermal properties of FNM generate sufficient heat and enhance ROS generation (about 5.5 times that during chemotherapy) to induce cell death, supporting photothermal therapy (PTT). These combined actions result in the evident death of both GSC and glioma cells, thereby improving the antitumor outcomes of GBM, as evidenced by significant glioma suppression and an approximately 115.38 % survival extension percentage of tumor-bearing nude mice. In conclusion, this dual-targeted drug delivery across the BBB presents a promising alternative strategy for glioma treatment.