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Efficient delivery of clay-based nanovaccines to the mouse spleen promotes potent anti-tumor immunity for both prevention and treatment of lymphoma

Abstract

Cancer therapeutic nanovaccines are ideal tools to inhibit tumor growth and provide the body with continuous protecting immune surveillance. However, the conventional subcutaneous (SC) vaccination normally induces limited anti-tumor immune responses with low therapeutic efficacy. Herein, we devised clay-based nanovaccines and directly delivered them to the spleen via intravenous (IV) injection to induce the stronger anti-tumor immunity with higher efficacy for tumor prevention and treatment. The clay, i.e., layered double hydroxide (LDH) was prepared as nanoadjuvant with the average size from 77 to 285 nm and co-loaded with the model antigen ovalbumin (OVA) and bioadjuvant CpG to form CpG/OVA-LDH (CO-LDH) nanovaccines. We found that CO-LDH-215 (the size of LDH was 215 nm) promoted dendritic cells to present the most antigen, and moreover showed the highest spleen enrichment (~ 1.67% of CO-LDH-215 enriched in the spleen at 24 h post IV injection). The in vivo immunologic data showed that CO-LDH-215 induced the most potent anti-tumor immune responses and completely prevented the growth of E.G7-OVA tumor in the mouse model. Furthermore, IV injected CO-LDH-215 nanovaccine more effectively delayed tumor growth than that SC injected, largely due to the direct and quick delivery of more nanovaccines to the spleen. This study demonstrates that the therapeutic efficacy of nanovaccines can be greatly enhanced by targeted delivery of nanovaccines to the spleen via the proper vaccination route.

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Acknowledgements

This work was financially supported by the International Partnership Program of Chinese Academy of Sciences (No. 122111KYSB20180005), the Australian Research Council (ARC) Discovery Project (No. DP190103486), Zhejiang Provincial Natural Science Foundation of China (No. LY19H160011), and Ningbo Digestive System Clinical Medicine Research Center (No. 2019A21003). We also thank the support from the Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province.

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Correspondence to Ting Cai, Rui-Tian Liu or Zhi Ping Xu.

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Efficient delivery of clay-based nanovaccines to the mouse spleen promotes potent anti-tumor immunity for both prevention and treatment of lymphoma

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Zhang, LX., Jia, YB., Huang, YR. et al. Efficient delivery of clay-based nanovaccines to the mouse spleen promotes potent anti-tumor immunity for both prevention and treatment of lymphoma. Nano Res. 14, 1326–1334 (2021). https://doi.org/10.1007/s12274-020-3175-0

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Keywords

  • cancer immunotherapy
  • nanovaccine
  • layered double hydroxide
  • targeted delivery to the spleen
  • lymphoma