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Yuba E, Sakaguchi N, Kanda Y, et al. pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity. Vaccines (Basel). 2017;5(4)doi: 10.3390/vaccines5040041.
Yuba, E., Sakaguchi, N., Kanda, Y., Miyazaki, M., & Koiwai, K. (2017). pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity. Vaccines, 5(4), . https://doi.org/10.3390/vaccines5040041
Yuba, Eiji, et al. "pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity." Vaccines vol. 5,4 (2017). doi: https://doi.org/10.3390/vaccines5040041
Yuba E, Sakaguchi N, Kanda Y, Miyazaki M, Koiwai K. pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity. Vaccines (Basel). 2017 Nov 04;5(4). doi: 10.3390/vaccines5040041. PMID: 29113042; PMCID: PMC5748608.
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Vaccines (Basel). 2017 Nov 04;5(4). doi: 10.3390/vaccines5040041.

pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity.

Vaccines

Eiji Yuba, Naoki Sakaguchi, Yuhei Kanda, Maiko Miyazaki, Kazunori Koiwai

Affiliations

  1. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. [email protected].
  2. Terumo Corp., Ashigarakami-gun, Kanagawa 2590151, Japan. [email protected].
  3. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. [email protected].
  4. Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. [email protected].
  5. Terumo Corp., Ashigarakami-gun, Kanagawa 2590151, Japan. [email protected].

PMID: 29113042 PMCID: PMC5748608 DOI: 10.3390/vaccines5040041

Abstract

(1) Background: Cytoplasmic delivery of antigens is crucial for the induction of cellular immunity, which is an important immune response for the treatment of cancer and infectious diseases. To date, fusogenic protein-incorporated liposomes and pH-responsive polymer-modified liposomes have been used to achieve cytoplasmic delivery of antigen via membrane rupture or fusion with endosomes. However, a more versatile cytoplasmic delivery system is desired for practical use. For this study, we developed pH-responsive micelles composed of dilauroyl phosphatidylcholine (DLPC) and deoxycholic acid and investigated their cytoplasmic delivery performance and immunity-inducing capability. (2) Methods: Interaction of micelles with fluorescence dye-loaded liposomes, intracellular distribution of micelles, and antigenic proteins were observed. Finally, antigen-specific cellular immune response was evaluated in vivo using ELIspot assay. (3) Results: Micelles induced leakage of contents from liposomes via lipid mixing at low pH. Micelles were taken up by dendritic cells mainly via macropinocytosis and delivered ovalbumin (OVA) into the cytosol. After intradermal injection of micelles and OVA, OVA-specific cellular immunity was induced in the spleen. (4) Conclusions: pH-responsive micelles composed of DLPC and deoxycholic acid are promising as enhancers of cytosol delivery of antigens and the induction capability of cellular immunity for the treatment of cancer immunotherapy and infectious diseases.

Keywords: cellular immunity; dendritic cell; deoxycholic acid; micelle; pH-responsive

Conflict of interest statement

The authors declare no conflict of interest.

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