A Stepwise-Enhanced Schottky Heterojunction Enables Ultra-Low-Dose Radiodynamic Therapy via Matrix Remodeling and...

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/Nb₂C@PEG Schottky heterojunction (HTNCP). Relying on the Nb₂C'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.