Low Dose Soft X‐Ray Remotely Triggered Lanthanide Nanovaccine for Deep Tissue CO Gas Release and Activation of Systemic Anti‐Tumor Immunoresponse

• Published in: Advanced science Vol. 8; no. 12; pp. e2004391 - n/a
• Main Authors: Li, Youbin, Jiang, Mingyang, Deng, Zhiming, Zeng, Songjun, Hao, Jianhua
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.06.2021; John Wiley and Sons Inc; Wiley
• Subjects: activated systemic anti‐tumor immunotherapy; Animals; Cancer therapies; Cancer Vaccines - immunology; Carbon Monoxide; Cell Line, Tumor; Cells, Cultured; Crystal lattices; Design; Disease Models, Animal; Efficiency; elicited tumor oxidative stress; gas therapy; Immunogenic Cell Death - drug effects; Immunogenic Cell Death - immunology; Immunology; Immunotherapy; lanthanide scintillator‐based nanovaccine; Lanthanoid Series Elements - pharmacology; Light; Mice; Nanoparticles; Neoplasms - immunology; Particle size; reversed immunosuppressive tumor microenvironment; soft X‐ray‐activated CO release; Spectrum analysis; Tumor Microenvironment - drug effects; Tumor Microenvironment - immunology; Tumors; X-Rays; gas therapy; elicited tumor oxidative stress; soft X-ray-activated CO release; lanthanide scintillator-based nanovaccine; reversed immunosuppressive tumor microenvironment; activated systemic anti-tumor immunotherapy
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202004391

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. A novel soft X‐ray remotely stimulated lanthanide scintillator‐based CO releasing system is designed. The nanovaccine presents efficient CO generation ability, which can further realize deep tissue gas therapy, activate a systemic anti‐tumor immune‐response, and reverse an immunosuppressive tumor microenvironment. The findings demonstrate a new strategy of designing anti‐tumor nanovaccines for soft X‐ray triggered deep tissue gas therapy and immune response.