Flexible deformation and special interface structure in nanoparticle-stabilized Pickering bubbles strengthen the immunological response as adjuvant†

Adjuvants can enhance an immunological response, which is an important part of vaccine research. Pickering bubbles have been a mega-hit for biomedical applications, including in vivo visualization and targeted drug delivery. However, there have been no studies on Pickering bubbles as an immunological adjuvant, and the special properties and structures of Pickering bubbles may play an important role in immunization. In this study, poly(lactic-co-glycolic acid) (PLGA) particles were used to construct nanoparticle-stabilized Pickering bubbles (PPBs). PPBs were evaluated as immunological adjuvants based on immune response effects and mechanisms and aiming at future applications. PPBs have a flexible gas core and a special surface structure that can increase the cell contact area to promote phagocytosis and enhance the immune response. Quartz crystal microbalance with dissipation (QCM-D) data showed the flexibility of PPBs, and confocal images captured the deformability of PPBs during cell uptake. Flow cytometry and antibody titer detection showed that PPBs significantly promoted antigen uptake and activation of bone-marrow-derived dendritic cells (BMDCs) and induced an immune response with upregulated SIINFEKL MHC I and CD127 molecules on the surface of CD8⁺ T cells, indicating excellent antigen cross-presentation and cellular immune triggering effects. The upregulation of CD44 and CD62L on CD4⁺ T cells and the IgG2a/IgG1 ratio bias further demonstrated the excellent adjuvant role of PPBs in immunity. Finally, the biosafety of PPBs as an immunological adjuvant was also demonstrated. Our study demonstrates the potential of particle-stabilized bubbles as immune adjuvants, which provides innovative ideas for vaccine development and design.