Internal medicine

Nuclear medicine

Mathematics

Statistics

Radiochemistry

Chemistry

Metallurgy

Materials science

Monte Carlo method

Thorium

Cancer research

Radiation therapy

Uranium

Medicine

Angewandte Chemie International Edition

High‐Z metal‐based nanoscale metal–organic frameworks (nMOFs) with photosensitizing ligands can enhance radiation damage to tumors via a unique radiotherapy‐radiodynamic therapy (RT‐RDT) process. Here we report Monte Carlo (MC) simulation‐guided design of a Th‐based nMOF built from Th 6 ‐oxo secondary building units and 5,15‐di(p‐benzoato)porphyrin (DBP) ligands, Th‐DBP, for enhanced RT‐RDT. MC simulations revealed that the Th‐lattice outperformed the Hf‐lattice in radiation dose enhancement owing to its higher mass attenuation coefficient. Upon X‐ray or γ‐ray radiation, Th‐DBP enhanced energy deposition, generated more reactive oxygen species, and induced significantly higher cytotoxicity to cancer cells over the previously reported Hf‐DBP nMOF. With low‐dose X‐ray irradiation, Th‐DBP suppressed tumor growth by 88 % in a colon cancer and 97 % in a pancreatic cancer mouse model.

Monte Carlo Simulation‐Guided Design of a Thorium‐Based Metal–Organic Framework for Efficient Radiotherapy‐Radiodynamic Therapy