Dual‐Heterojunctions with Reversibly Photoactivated Structure Shift Alternately Decode Photocatalytic H <sub>2</sub> Burst and Cascade Catalytic ROS Birth to Repress Cancer
Duo Wang, Guanhua Qiu, Hong Wang, Liyao Zheng, Xiaoqian Zhang, Zelun Li, Maocheng Zuo, Xiaobo Wang, Niqiang Zhou, Lujia Xiao, Junjie Liu, Tao Luo, Sijia Liu, Kun Zhang
Abstract
Abstract Single or combined ROS therapy will induce cancer resistance after long‐term medication cure. Although currently concurrent H 2 /ROS therapy is a promising method, the mutual reaction between H 2 and ROS dampens their efficiency. To address this issue, g‐C 3 N 4 ‐based dual‐heterojunctions, i.e., N‐doped carbon nanoribbons (N‐CNB)/g‐C 3 N 4 and core–shell‐structured Au@Pd nanoparticles/g‐C 3 N 4 , respectively, are constructed to decode alternate H 2 /ROS therapy. Therein, N‐CNB/g‐C 3 N 4 heterojunctions enhance near‐infrared (NIR) photoabsorption to unlock photocatalytic H 2 evolution, and Au@Pd/g‐C 3 N 4 heterojunctions unlock the inherent and newly‐emerging bioenzymes‐like catalytic ROS birth. In this alternate H 2 /ROS therapy, photocatalytic H 2 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 H 2 /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.