Neutrophil Delivered Hollow Titania Covered Persistent Luminescent Nanosensitizer for Ultrosound Augmented Chemo/Immuno Glioblastoma Therapy

Glioblastoma (GBM) is the most malignant brain tumor with unmet therapeutic demand. The blood‐brain‐barrier (BBB) and tumor heterogeneity limit the treatment effectiveness of various interventions. Here, an ultrasound augmented chemo/immuno therapy for GBM using a neutrophil‐delivered nanosensitizer, is developed. The sensitizer is composed of a ZnGa2O4:Cr3+ (ZGO) core for persistent luminescence imaging and a hollow sono‐sensitive TiO2 shell to generate reactive oxygen species (ROS) for controlled drug release. Immune checkpoint inhibitor (Anti‐PD‐1 antibody) is trapped in the interior of the porous ZGO@TiO2 with paclitaxel (PTX) loaded liposome encapsulation to form ZGO@TiO2@ALP. Delivered by neutrophils (NEs), ZGO@TiO2@ALP‐NEs can penetrate through BBB for GBM accumulation. After intravenous injection, ultrasound irradiation at GBM sites initiates ROS generation from ZGO@TiO2@ALP, leading to liposome destruction for PTX and anti‐PD‐1 antibody release to kill tumors and induce local inflammation, which in‐turn attractes more ZGO@TiO2@ALP‐NEs to migrate into tumor sites for augmented and sustained therapy. The treatment enhances the survival rate of the GBM bearing mice from 0% to 40% and endows them with long‐term immuno‐surveillance for tumor recurrence, providing a new approach for precision therapy against GBM and other cancers. Delivered by neutrophils (NEs), ZGO@TiO2@ALP‐NEs can penetrate through blood‐brain‐barrier for glioblastoma (GBM) accumulation. Ultrasound irradiation at GBM sites initiates generate reactive oxygen species generation from ZGO@TiO2@ALP, leading to liposome destruction for paclitaxel and anti‐PD‐1 antibody release to kill tumor and induce local inflammation, which in‐turn attracts more ZGO@TiO2@ALP‐NEs for augmented and sustained tumor elimination.