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Vaccines 2017, 5(4), 41; doi:10.3390/vaccines5040041

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

1
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1–1 Gakuen–cho, Naka–ku, Sakai, Osaka 5998531, Japan
2
Terumo Corp., Ashigarakami–gun, Kanagawa 2590151, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Rachel L. Roper
Received: 3 October 2017 / Revised: 31 October 2017 / Accepted: 3 November 2017 / Published: 4 November 2017
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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. View Full-Text
Keywords: micelle; pH-responsive; deoxycholic acid; dendritic cell; cellular immunity micelle; pH-responsive; deoxycholic acid; dendritic cell; cellular immunity
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MDPI and ACS Style

Yuba, E.; Sakaguchi, N.; Kanda, Y.; Miyazaki, M.; Koiwai, K. pH-Responsive Micelle-Based Cytoplasmic Delivery System for Induction of Cellular Immunity. Vaccines 2017, 5, 41.

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