DNA-loaded nano-adjuvant formed with a vitamin E-scaffold intracellular environmentally-responsive lipid-like material for cancer immunotherapy

Nanomedicine : Nanotechnology, Biology, and Medicine
Minori KawaiHidetaka Akita

Abstract

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-β 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.

Citations

Apr 3, 2020·Biological & Pharmaceutical Bulletin·Ikramy A KhalilHideyoshi Harashima
May 28, 2019·Pharmaceutics·Juan I BussioJosé Vicente González-Aramundiz
Jan 11, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Seigo KimuraHideyoshi Harashima
Dec 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yusuke SatoHideyoshi Harashima
Feb 17, 2019·Acta Biomaterialia·David G LeachJeffrey D Hartgerink
Sep 12, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yuma YamadaHideyoshi Harashima
Jun 3, 2021·Pharmaceutics·Saed Abbasi, Satoshi Uchida
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Safiye AkkınErem Bilensoy

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