Menthol nanoliposomes enhanced anti-tumor immunotherapy by increasing lymph node homing of dendritic cell vaccines.

Menthol, a cyclic terpene alcohol, plays a critical role in overcoming the blood-brain barrier and stratum corneum barrier. Herein, we innovatively propose a menthol nanoliposome (Men-nanoLips) that can dramatically increase lymph node accumulation of the dendritic cell (DC)-based anti-tumor vaccines. Specifically, Men-nanoLips efficiently enhanced lymphatic endothelial cell (EC) barrier permeability by reducing the expression of tight junction proteins. And interestingly, Men-nanoLips not only up-regulated the expression of CCR7 in DCs but also increased the secretion of CCL21 in lymphatic ECs. Moreover, Men-nanoLips promoted DC vaccine maturation as evidenced by increasing the expression of costimulatory molecules and up-regulating the pseudopodia-like protein. With those complementary mechanisms provided by Men-nanoLips, the number of the B16 whole-tumor cell lysate-loaded DCs that target the draining LN enhanced remarkably and significantly boosted the treatment efficacy of DC anti-tumor vaccines. Therefore, we concluded that Men-nanoLips could be instructive for increasing LN homing of DC vaccines.