The impact of size for liposomes modified with pH-responsive β-glucan derivatives on the initiation of cellular and humoral immune responses in murine models

Abstract

Size is one of the important factors for antigen carriers because it influences cellular interaction, pharmacokinetics, immune cell activation and the types of immune responses. We developed pH-sensitive polysaccharide derivative-modified liposomes as antigen carriers for induction of antigen-specific immune responses. For an earlier study, the size of these liposomes was controlled to within 100–200 nm considering the suitable size for endocytosis. However, since most antigen-presenting cells can engulf larger particles, the proper liposome size and its effect on the induction of cellular versus humoral immune responses remains unclear. Here, we examined the effects of polysaccharide derivative-modified liposome size on immune responses. Liposome size was controlled by using an extrusion method by passing liposomes through a polycarbonate membrane of different pore sizes. Small liposomes encapsulating model antigenic protein suppressed antigen-expressing tumour growth effectively and increased the IgG2a/IgG1 ratio early after liposome administration, suggesting that Th1 response was mainly induced. Large liposomes increased antigen-specific IgG1 and IgG2a production for 56 days compared with small liposomes. These results suggest that small liposomes modified with pH-responsive polysaccharide derivatives could be effective for cancer immunotherapy whereas large liposomes could be suitable for induction of antibody production towards vaccination.

Keywords:

• Liposome
• particle size
• polysaccharide
• antibody production
• antitumour effect
• immune response

Acknowledgment

The authors appreciate Maki Ohashi (Sanyo Fine Co., Ltd., Osaka, Japan) for his kind support in providing Aquaβ.

Authors’ contribution

Conceptualization, S.Y. and E.Y.; methodology, S.Y.; validation, E.Y.; formal analysis, S.Y.; investigation, S.Y.; data curation, E.Y. and A.H.; writing—original draft preparation, S.Y. and E.Y.; writing—review and editing, E.Y.; visualization, S.Y.; supervision, E.Y.; project administration, E.Y.; funding acquisition, E.Y. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

The authors declare no conflict of interest.

Institutional review board statement

The animal study protocol was approved by the Institutional Review Board of Osaka Prefecture University (protocol code No. 22-1, April 1, 2022).

Data availability statement

All data needed to evaluate the conclusions in the article are present in the article and/or the Supplementary Materials. Additional data are available from the corresponding author [E.Y.] upon reasonable request.

Additional information

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number JP21H03822 and JP23H04087.