Engineering the Deformability of Albumin-Stabilized Emulsions for Lymph-Node Vaccine Delivery

A major challenge in vaccine delivery is to achieve robust lymph-node (LN) accumulation, which can capitalize on concentrated immunocytes and cytokines in LNs to stimulate the onset and persistence of adaptive immune responses. Previous attempts at developing vaccine delivery systems have focused on the sizes, charges, or surface ligands but not on their deformability. In fact, the LN homing of antigen-presenting cells depends on deformability to pass through the cellular gaps. Herein, the deformability of albumin-stabilized emulsions is engineered. Owing to self-adaptive deformability, the droplets (≈330 nm) can attach to and deform between cells and adjust their sizes to pass through the endothelial gaps (20-100 nm), favoring direct LN transfer (intercellular pathway). Additionally, owing to relatively large sizes, some emulsions can be retained at the administration sites for potent antigen uptake and activation of APCs as well as LN-targeted delivery of vaccines (intracellular pathway). Compared with solid particles, the dual LN transfer strategy evidently enhances antigen accumulation and activation of LN drainage, potently stimulates cellular immune responses, and increases the survival rate of tumor-bearing mice. Thus, the deformability of albumin-stabilized droplets may offer an efficient strategy for potent LN targeting and enhanced vaccinations.