LAUSR

Abstract Intratumoral immunosuppressive microenvironment (ISM) remains the dominant limitation to disable oncological immunotherapy such as immunogenic cell death (ICD). To resolve the immune escape, a sonodynamic therapy (SDT)-based nanoplatform featuring continuous CO2 bubbling has been engineered to enforce continuous ultrasound-triggered inertial cavitation (UIC) for augmenting ROS production. Systematic in vitro and in vivo results demonstrate that the continuous UIC expedites massive production of reactive oxygen species (ROS), consequently enabling multiple enhancements of SDT under only one administration. More significantly, the highly-accumulative ROS arising from continuous UIC have been demonstrated to induce robust ICD that is typically represented by more antigen exposure and presentation, augmented DCs maturation and more activated effector CD8+ T cells infiltration in vitro & in vivo. Concurrently, the most ISM alleviation via releasing more pro-inflammatory cytokines and facilitating pro-tumorigenic M2-like macrophage polarization into anti-tumorigenic M1-like counterparts is accompanied, enabling immune escape blockade. Contributed by the significant ISM alleviation and massive ROS production for enhancing SDT and ICD, such SDT-based composite nanoplatforms harvest the most substantially enhanced inhibitory consequences against primary and metastatic tumors, which, thus, provide a profound attribute for T cell-based immunotherapy against tumor.