期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 14, 期 8, 页码 2587-2597出版社
ELSEVIER
DOI: 10.1016/j.nano.2018.08.006
关键词
Cancer immunotherapy; DNA; Adjuvant; ssPalm; Intracellular trafficking
资金
- JSPS KAKENHI [15H01806, 18K18377]
- JST CREST [JPMJCR17H1]
- Asahi Glass Foundation
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [15H01806, 18K18377] Funding Source: KAKEN
Cytoplasmic DNA triggers cellular immunity via activating the stimulator of interferon genes pathway. Since DNA is degradable and membrane impermeable, delivery system would permit cytoplasmic delivery by destabilizing the endosomal membrane for the use as an adjuvant. Herein, we report on the development of a plasmid DNA (pDNA)-encapsulating lipid nanoparticle (LNP). The structural components include an SS-cleavable and pH-activated lipid-like material that mounts vitamin E as a hydrophobic scaffold, and dual sensing motifs that are responsive to the intracellular environment (ssPalmE). The pDNA-encapsulating LNP (ssPalmE-LNP) induced a high interferon-beta production in Raw 264.7 cells. The subcutaneous injection of ssPalmE-LNP strongly enhanced antigen-specific cytotoxic T cell activity. The ssPalmE-LNP treatment efficiently induced antitumor effects against E. G7-OVA tumor and B16-F10 melanoma metastasis. Furthermore, when combined with an anti-programmed death 1 antibody, an extensive therapeutic antitumor effect was observed. Therefore, the ssPalmE-LNP is a promising carrier of adjuvants for cancer immunotherapy. (c) 2018 Elsevier Inc. All rights reserved.
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