Radial porous SiO₂ nanoflowers potentiate the effect of antigen/adjuvant in antitumor immunotherapy

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.

Graphical abstract

Keywords

silica nanoflower / antigen delivery / cancer immunotherapy / nanovaccine

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Acknowledgements

The authors thank for the National Natural Science Foundation of China (Grant No. 81972899), Natural Science Foundation of Tianjin City (Grant No. 18JCQNJC14500), CAMS Innovation Fund for Medical Sciences (Grant No. 2017-I2M-3-022), Specific Program for High-Tech Leader&Team of Tianjin Government, Tianjin innovation and promotion plan key innovation team of immunoreactive biomaterials. The authors declare that they have no conflict of interest.

Electronic Supplementary Material

Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11705-020-2034-6 and is accessible for authorized users.

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