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Radial porous SiO2 nanoflowers potentiate the effect of antigen/adjuvant in antitumor immunotherapy
Authors:Chuangnian Zhang  Ying Dong  Jing Gao  Xiaoli Wang  Yanjun Jiang
Affiliation:1. Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China2. School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, China
Abstract:Here, we reported a cancer nanovaccine based on SiO2 nanoflowers with a special radial pore structure, which greatly enhanced cross-presentation and induced the production of cytotoxic T lymphocyte cells secreting granzymes B and interferon-γ. The antigen ovalbumin was covalently conjugated onto the as-synthesized hierarchical SiO2 nanoflowers, and the adjuvant cytosine-phosphate-guanine was electrostatically adsorbed into their radial pore by simple mixing before use. The nanovaccine exhibited excellent storage stability without antigen release after 27 days of incubation, negligible cytotoxicity to dendritic cells, and a high antigen loading capacity of 430 ± 66 mg·g−1 support. Besides, the nanovaccine could be internalized by dendritic cells via multiple pathways. And the enhancement of antigen/adjuvant uptake and lysosome escape of antigen were observed. Noteworthy, in vitro culture of bone marrow-derived dendritic cells in the presence of nanovaccine proved the activation of dendritic cells and antigen cross-presentation as well as secretion of proinflammatory cytokines. Besides, in vivo study verified the targeting of nanovaccine to draining lymph nodes, the complete suppression of tumor in six out of ten mice, and the triggering of notable tumor growth delay. Overall, the present results indicated that the nanovaccine can be served as a potential therapeutic vaccine to treat cancer.
Keywords:silica nanoflower  antigen delivery  cancer immunotherapy  nanovaccine  
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