pH-Sensitive branched beta-glucan-modified liposomes for activation of antigen presenting cells and induction of antitumor immunity

Induction of cellular immunity is important for effective cancer immunotherapy. Although various antigen carriers for cancer immunotherapy have been developed to date, balancing efficient antigen delivery to antigen presenting cells (APCs) and their activation via innate immune receptors, both of which are crucially important for the induction of strong cellular immunity, remains challenging. For this study, branched beta-glucan was selected as an intrinsically immunity-stimulating and biocompatible material. It was engineered to develop multifunctional liposomal cancer vaccines capable of efficient interactions with APCs and subsequent activation of the cells. Hydroxy groups of branched beta-glucan (Aqua beta) were modified with 3-methylglutaric acid ester and decyl groups, respectively, to provide pH-sensitivity and anchoring capability to the liposomal membrane. The modification efficiency of Aqua beta derivatives to the liposomes was significantly high compared with linear beta-glucan (curdlan) derivatives. Aqua beta derivative-modified liposomes released their contents in response to weakly acidic pH. As a model antigenic protein, ovalbumin (OVA)-loaded liposomes modified with Aqua beta derivatives interacted efficiently with dendritic cells, and induced inflammatory cytokine secretion from the cells. Subcutaneous administration of Aqua beta derivative-modified liposomes suppressed the growth of the E.G7-OVA tumor significantly compared with curdlan derivative-modified liposomes. Aqua beta derivative-modified liposomes induced the increase of CD8(+) T cells, and polarized macrophages to the antitumor M1-phenotype within the tumor microenvironment. Therefore, pH-sensitive Aqua beta derivatives can be promising materials for liposomal antigen delivery systems to induce antitumor immune responses efficiently.

Automated summary

The study utilized branched beta-glucan as a naturally immune-stimulating and biocompatible material to develop multifunctional liposomal cancer vaccines that efficiently interacted with APCs and activated cells. The Aqua beta derivative-modified liposomes were pH-sensitive and capable of releasing their contents in response to weakly acidic pH, leading to efficient interaction with dendritic cells and induction of antitumor immune responses within the tumor microenvironment.