4.8 Article

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

Journal

NANO RESEARCH
Volume 14, Issue 5, Pages 1326-1334

Publisher

TSINGHUA UNIV PRESS
DOI: 10.1007/s12274-020-3175-0

Keywords

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

Funding

  1. International Partnership Program of Chinese Academy of Sciences [122111KYSB20180005]
  2. Australian Research Council (ARC) Discovery Project [DP190103486]
  3. Zhejiang Provincial Natural Science Foundation of China [LY19H160011]
  4. Ningbo Digestive System Clinical Medicine Research Center [2019A21003]
  5. Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province

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The study demonstrates that targeted delivery of CO-LDH-215 nanovaccines to the spleen significantly enhances the therapeutic efficacy of nanovaccines and induces stronger anti-tumor immune responses. This nanovaccine effectively delays tumor growth and completely prevents the development of E.G7-OVA tumors in a mouse model.
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 (similar to 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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