期刊
ADVANCED SCIENCE
卷 8, 期 12, 页码 -出版社
WILEY
DOI: 10.1002/advs.202004391
关键词
activated systemic anti‐ tumor immunotherapy; elicited tumor oxidative stress; gas therapy; lanthanide scintillator‐ based nanovaccine; reversed immunosuppressive tumor microenvironment; soft X‐ ray‐ activated CO release
资金
- National Natural Science Foundation of China [21671064]
- Science and Technology Planning Project of Hunan Province [2017RS3031]
- Scientific Research Fund of Hunan Provincial Education Department [19A329]
- Natural Science Foundation of Hunan Province, China [2019JJ10002]
- Hunan Provincial Innovation Foundation for Postgraduate [CX20190338]
- Furong Scholars Programme of Hunan Province
Gas-based therapy has been used for anti-tumor treatment, but its efficacy is limited by factors such as deep tissue controlled release and poor lymphocytic infiltration. A new type of nanovaccine is designed to generate CO gas through soft X-ray irradiation, reversing the immunosuppressive TME and activating anti-tumor immunity. This design inhibits tumor growth locally and distally through a systemic anti-tumor immunoresponse activated by soft X-ray irradiation.
Gas-based therapy has emerged as a new green therapy strategy for anti-tumor treatment. However, the therapeutic efficacy is still restricted by the deep tissue controlled release, poor lymphocytic infiltration, and inherent immunosuppressive tumor microenvironment (TME). Herein, a new type of nanovaccine is designed by integrating low dose soft X-ray-triggered CO releasing lanthanide scintillator nanoparticles (ScNPs: NaLuF4:Gd,Tb@NaLuF4) with photo-responsive CO releasing moiety (PhotoCORM) for synergistic CO gas/immuno-therapy of tumors. The designed nanovaccine presents significantly boosted radioluminescence and enables deep tissue CO generation at unprecedented tissue depths of 5 cm under soft X-ray irradiation. Intriguingly, CO as a superior immunogenic cell death (ICD) inducer further reverses the deep tissue immunosuppressive TME and concurrently activates adaptive anti-tumor immunity through efficient reactive oxygen species (ROS) generation. More importantly, the designed nanovaccine presents efficient growth inhibition of both local and distant tumors via a soft X-ray activated systemic anti-tumor immunoresponse. This work provides a new strategy of designing anti-tumor nanovaccines for synergistic deep tissue gas-therapy and remote soft X-ray photoactivation of the immune response.
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