Piezo/photo-catalytic nano-actuators modulating mechanical force for mechanosensitive anti-tumor immunotherapy

In cancer, the infiltration of immune cells is significantly impeded by aberrantly elevated tumor interstitial fluid pressure (TIFP, a typical mechanical force). For reducing TIFP to augment immunoinfiltration, we synthesized a Fe-doped crystalline carbon nitride as nano-actuators (CFL@M), which can effectively reduce TIFP by piezo/photo-catalytically interstitial fluid splitting. As the mechanical forces change in tumors (TIFP decreased to 60.79%), the trafficking of immune cells into deep tumor tissue were notably facilitated. Among them, the infiltration of dendritic cells was enhanced by 13.02%, and that of M1-type macrophages was enhanced by 30.34%. Moreover, CD4⁺ T cells and CD8⁺ T cells responded to changes of fluid pressure by aggregating towards the tumor center. Therefore, the nano-actuators provide a promising mechanosensitive immunotherapy by reducing interstitial fluid pressure to sustain an effective infiltration of immune cells, which results in significant therapeutic benefits such as retarded tumor growth (72.6%), inhibited tumor metastasis (76.56%) and extended survivals. Briefly, this nano-actuator with good biosafety is a new endeavor in the field of “mechano-immunology”.