Fig. 1. Schematic of enhanced anti-glioblastoma efficacy using combinatory immunotherapy of CAR-neutrophils and tumor microenvironment responsive nanodrugs.

a Human pluripotent stem cells were engineered with CARs and differentiated into CAR-neutrophils that are loaded with rough silica nanoparticles (SiO₂ NPs) containing hypoxia-targeting tirapazamine (TPZ) or other drugs, as a dual immunochemotherapy. b Systemically administered CAR-neutrophil@R-SiO₂-TPZ NPs first attack external normoxic tumor cells by forming immunological synapses and kill tumor cells via phagocytosis. After apoptosis, CAR-neutrophils could then release R-SiO₂-TPZ NPs, which are uptaken by tumor cells. Afterwards, nano-prodrugs respond to the hypoxic tumor microenvironment and effectively kill tumor cells. TEOS tetraethyl orthosilicate, BTES bis[3-(triethoxysilyl) propyl] tetrasulfide, TPZ tirapazamine, BTZ benzotriazinyl.