Dual-Heterojunctions with Reversibly Photoactivated Structure Shift Alternately Decode Photocatalytic H2 Burst and Cascade Catalytic ROS Birth to Repress Cancer.

Single or combined ROS therapy will induce cancer resistance after long-term medication cure. Although currently concurrent H2/ROS therapy is a promising method, the mutual reaction between H2 and ROS dampens their efficiency. To address this issue, g-C3N4-based dual-heterojunctions, i.e., N-doped carbon nanoribbons (N-CNB)/g-C3N4 and core-shell-structured Au@Pd nanoparticles/g-C3N4, respectively, are constructed to decode alternate H2/ROS therapy. Therein, N-CNB/g-C3N4 heterojunctions enhance near-infrared (NIR) photoabsorption to unlock photocatalytic H2 evolution, and Au@Pd/g-C3N4 heterojunctions unlock the inherent and newly-emerging bioenzymes-like catalytic ROS birth. In this alternate H2/ROS therapy, photocatalytic H2 evolution and multienzymically-catalytic ROS birth are alternately decoded under NIR "on" and "off", respectively, because the photoirradiation-triggered structural shift insensitive to photothermal effects is reversible in response to NIR "on" and "off", displaying a temporal controllability. The alternate H2/ROS therapy expedites the infiltrations and intratumoral proliferation of anti-tumor immune cells including CTLs and Th17, hampers the infiltrations of exhausted CD8+ T cells and Tregs, and downregulates resistance-associated proteins (PARP, EpCAM, and CD133). These actions cooperatively activate robust immune responses, attenuate anti-tumor immunity confinements, and cancer resistance to suppress common and Sorafenib-induced resistant liver cancer. This work offers distinctive insights into cancer resistance removal.