4.8 Article

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

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 61, Issue 46, Pages -

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202208685

Keywords

Metal-Organic Framework; Monte Carlo Simulation; Radiodynamic Therapy; Radiotherapy

Funding

  1. National Cancer Institute [U01-CA198989, 1R01CA253655]
  2. University of Chicago Medicine Comprehensive Cancer Center (NIH CCSG) [P30 CA014599]

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This study reported a metal-based nanoscale metal-organic framework (nMOF) built from thorium and photosensitizing ligands for enhanced radiation damage to tumors. Monte Carlo simulations showed that the thorium lattice outperformed other lattices in radiation dose enhancement. Experimental results demonstrated that the nMOF generated more reactive oxygen species and induced higher cytotoxicity to cancer cells under X-ray or gamma-ray radiation. In mouse models, the nMOF significantly suppressed tumor growth under low-dose X-ray irradiation.
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 gamma-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.

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