Chemical Engineering Journal, 15 September, 2025, DOI：https://doi.org/10.1016/j.cej.2025.165056

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

Cong Cong, Xuejiao J. Gao, Fei Ye, Xuwu Zhang, Yuchu He, Zhenhe Ma, Wenkang Tu, Weili Xue, Kelong Fan, Dawei Gao

Abstract

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”.

Article link：https://www.sciencedirect.com/science/article/pii/S1385894725058929?via%3Dihub