Nanomedicine-unlocked radiofrequency dynamic therapy dampens incomplete radiofrequency ablation-arised immunosuppression to suppress cancer relapse.

Incomplete radiofrequency ablation (iRFA) not only leaves residual tumor, but also render the residual tumor highly self-adaptable and immunosuppressive, consequently expediting residual tumor progression including relapse. To address it, radiofrequency dynamic therapy (RFDT) with identical trigger (namely radiofrequency) has been established and enabled by polyethylene glycol (PEG)-modified Fe-based single atom nanozyme (P@Fe SAZ). P@Fe SAZ can respond to radiofrequency field to produce reactive oxygen species (ROS), attaining the nanomedicine-unlocked low-temperature RFDT. Systematic experiments reveal that ROS further remodels iRFA-potentiated immunosuppressive microenvironment, e.g., expediting tumor-associated macrophages (TAMs) polarization into TAMs-M1, rejecting the intratumoral infiltrations of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). Coincidently, they have been demonstrated to stimulate dendritic cells (DCs) maturation and encourage the proliferations and infiltrations of effector T cells, consequently boosting anti-tumor immune responses and attenuating iRFA-enhanced plasticity, treatment resistance and self-adaptation of residual hepatocellular carcinoma (HCC) after iRFA. Thanks to them, such a nanomedicine-unlocked low-temperature RFDT exerts powerful actions on residual HCC model after iRFA with rapid expansion inhibition, relapse repression, survival prolongation, apoptosis promotion, etc. This low-temperature RFDT opens a window to address the iRFA-enhanced immunosuppression.