Engineering W/O/W pickering emulsion for the enhanced antigen delivery and immune responses

Tumor immunotherapy, particularly cancer vaccines, holds promise for combating cancer by harnessing tailored immune responses against malignant cells. However, conventional approaches face challenges in efficiently delivering antigens for optimal immune activation. Emulsion adjuvants, like MF59, enhance cellular uptake but struggle to induce robust CD8⁺ T cell responses. Here, we introduce a novel strategy employing a water-in-oil-in-water (W/O/W) multiple Pickering emulsion (mPE) for antigen delivery. The mPE, utilizing biocompatible, pH-sensitive particles, encapsulates antigens within the inner water phase, ensuring enhanced intracellular processing and dictating the intracellular fate of antigens for improved cross-presentation. In vitro and in vivo studies demonstrated that mPEs induced robust dendritic cells activation and antigen cross-presentation, leading to a significantly enhanced immune response. Notably, calcium phosphate-stabilized mPE (CaP-mPE) illustrated the more robust IFN-γ⁺ T cell responses. In comparison with traditional surfactant-stabilized multiple emulsions, CaP-mPE significantly inhibit tumor growth and effectively prolong the survival of tumor-bearing mice. This innovative approach offers a promising avenue for the development of effective cancer vaccines with potent cellular immune responses.