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

Angew Chem Int Ed Engl. 2022 Nov 14;61(46):e202208685. doi: 10.1002/anie.202208685. Epub 2022 Oct 17.

Abstract

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 Th6 -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.

Keywords: Metal-Organic Framework; Monte Carlo Simulation; Radiodynamic Therapy; Radiotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Colonic Neoplasms* / drug therapy
  • Ligands
  • Metal-Organic Frameworks* / radiation effects
  • Metal-Organic Frameworks* / therapeutic use
  • Mice
  • Monte Carlo Method
  • Nanostructures* / therapeutic use
  • Thorium

Substances

  • Metal-Organic Frameworks
  • Thorium
  • Ligands