期刊
ADVANCED SCIENCE
卷 8, 期 17, 页码 -出版社
WILEY
DOI: 10.1002/advs.202004381
关键词
glioblastoma; multimodal therapy; persistent luminescent phosphor; titanium dioxide; ultrasound
资金
- National Natural Science Foundation of China [22034004, 21621003]
- Strategic Priority Research Program of Chinese Academy of Sciences [XDB36000000]
- Tsinghua University Spring Breeze Fund [2020Z99CFZ019]
An ultrasound augmented chemo/immuno therapy for GBM using a neutrophil-delivered nanosensitizer has been developed, which enhances the survival rate of GBM bearing mice and provides long-term immuno-surveillance for tumor recurrence. This new approach involves ROS generation from the sensitizer and liposome destruction for drug release to kill tumors and induce local inflammation.
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.
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