Cationic lipid potentiated the adjuvanticity of polysaccharide derivative-modified liposome vaccines

Eiji Yuba; Yuna Kado; Nozomi Kasho; Atsushi Harada

doi:10.1016/j.jconrel.2022.10.016

Cationic lipid potentiated the adjuvanticity of polysaccharide derivative-modified liposome vaccines

J Control Release. 2023 Oct:362:767-776. doi: 10.1016/j.jconrel.2022.10.016. Epub 2022 Oct 31.

Authors

Eiji Yuba¹, Yuna Kado², Nozomi Kasho², Atsushi Harada³

Affiliations

¹ Department of Applied Chemistry, Graduate School of Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan; Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. Electronic address: yuba@omu.ac.jp.
² Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan.
³ Department of Applied Chemistry, Graduate School of Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan; Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 5998531, Japan. Electronic address: atsushi_harada@omu.ac.jp.

PMID: 36244508
DOI: 10.1016/j.jconrel.2022.10.016

Abstract

Antigen carriers that can selectively deliver antigens to antigen presenting cells and which can simultaneously activate these cells (adjuvant property) are necessary for efficient cancer immunotherapy or vaccination. Delivery of a model antigen into dendritic cell cytosol has been achieved by pH-responsive polymer-modified liposomes via destabilization of endosomal membranes responding to acidic pH, which impelled antigen-specific cellular immunity. Furthermore, β-glucan-based pH-responsive polysaccharides have shown not only cytosolic antigen delivery performance but also adjuvant property, which further heightened cellular immune responses. Because pH-responsive polysaccharides have anionic carboxy groups, cationic lipid was introduced to liposomes in this study to improve the modification efficiency of pH-responsive polysaccharides and to improve their adjuvanticity and immunity-inducing functions. Introduction of cationic lipids increased the amounts of polysaccharide derivatives on the liposome and increased the cellular association of the liposomes to dendritic cells. Liposomes containing β-glucan-based pH-responsive polysaccharides and cationic lipids increased cytokine production from dendritic cells much more than other polysaccharide derivatives did. Furthermore, through improvement of intra-tumoral immunosuppression and induction of antigen-specific cellular immunity, administering these liposomes impelled tumor suppression even with a small antigen dose. These results suggest that introducing cationic lipids and using pH-responsive polysaccharides having intrinsically adjuvant function are effective for producing liposomal nanovaccines showing strong immunity-inducing function.

Keywords: Adjuvant; Cationic lipid; Dendritic cell; Liposome; Polysaccharide; β-glucan.