A Stepwise‐Enhanced Schottky Heterojunction Enables Ultra‐Low‐Dose Radiodynamic Therapy via Matrix Remodeling and Electron–Hole Separation

ABSTRACT Radiodynamic therapy (RDT) enhances the production of reactive oxygen species (ROS), thereby reducing clinical radiotherapy doses. Nanoscale metal–organic frameworks (nMOFs) based on high‐Z secondary building units (SBUs) and photosensitizing ligands have been developed to perform RDT. However, the rapid recombination of electron–holes reduces RDT efficiency, and an abundant matrix prevents nMOFs penetration into tumors. In this study, we combine heterojunction engineering with nMOFs‐based RDT for the first time to prepare an Hf‐TCPP/Nb 2 C@PEG Schottky heterojunction (HTNCP). Relying on the Nb 2 C's exceptional electrons absorption and photothermal conversion, HTNCP not only promotes electron–hole separation in Hf‐TCPP, boosting superoxide radical and singlet oxygen production by 2.64‐fold, but also utilizes a mild photothermal effect to degrade the collagen matrix to promote self‐penetration. Through sequential treatment involving irradiation 1064 nm laser and X‐ray, HTNCP can suppress the growth and metastasis of triple‐negative breast cancer tumors in mice using ultra‐low‐dose X‐ray (1 Gy × 5). This novel radiosensitizer displays excellent RDT efficacy and provides a universal sequential treatment strategy of “matrix degradation–RDT killing” for clinical tumor radiotherapy.