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

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2022 Sep 23

PMID 36149753

Authors

Ziwan Xu

Taokun Luo

Jianming Mao

Caroline McCleary

Eric Yuan

Wenbin Lin

Affiliations

Soon will be listed here.

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 Th -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.

Citing Articles

Nitric Oxide-Releasing Nanoscale Metal-Organic Layer Overcomes Hypoxia and Reactive Oxygen Species Diffusion Barriers to Enhance Cancer Radiotherapy.

Xiong Y, Li J, Jiang X, Zhen W, Ma X, Lin W Adv Sci (Weinh). 2025; 12(8):e2413518.

PMID: 39742392 PMC: 11848595. DOI: 10.1002/advs.202413518.

Ca- and cGAMP-Contained Semiconducting Polymer Nanomessengers for Radiodynamic-Activated Calcium Overload and Immunotherapy.

Cheng D, Luo L, Zhang Q, Song Z, Zhan Y, Tu W Adv Sci (Weinh). 2024; 12(6):e2411739.

PMID: 39679909 PMC: 11809400. DOI: 10.1002/advs.202411739.

Recent advances in the development of tumor microenvironment-activatable nanomotors for deep tumor penetration.

Jiang Q, He J, Zhang H, Chi H, Shi Y, Xu X Mater Today Bio. 2024; 27:101119.

PMID: 38966042 PMC: 11222818. DOI: 10.1016/j.mtbio.2024.101119.

STING agonist-conjugated metal-organic framework induces artificial leukocytoid structures and immune hotspots for systemic antitumor responses.

Luo T, Jiang X, Fan Y, Yuan E, Li J, Tillman L Natl Sci Rev. 2024; 11(7):nwae167.

PMID: 38887543 PMC: 11182667. DOI: 10.1093/nsr/nwae167.

Selenium-Doped Nanoheterojunctions for Highly Efficient Cancer Radiosensitization.

Qiao R, Yuan Z, Yang M, Tang Z, He L, Chen T Adv Sci (Weinh). 2024; 11(29):e2402039.

PMID: 38828705 PMC: 11304322. DOI: 10.1002/advs.202402039.

References

Martinov M, Thomson R . Technical Note: Taking EGSnrc to new lows: Development of egs++ lattice geometry and testing with microscopic geometries. Med Phys. 2020; 47(7):3225-3232. DOI: 10.1002/mp.14172. View

Bonvalot S, Rutkowski P, Thariat J, Carrere S, Ducassou A, Sunyach M . NBTXR3, a first-in-class radioenhancer hafnium oxide nanoparticle, plus radiotherapy versus radiotherapy alone in patients with locally advanced soft-tissue sarcoma (Act.In.Sarc): a multicentre, phase 2-3, randomised, controlled trial. Lancet Oncol. 2019; 20(8):1148-1159. DOI: 10.1016/S1470-2045(19)30326-2. View

Wan C, Sun Y, Tian Y, Lu L, Dai X, Meng J . Irradiated tumor cell-derived microparticles mediate tumor eradication via cell killing and immune reprogramming. Sci Adv. 2020; 6(13):eaay9789. PMC: 7096163. DOI: 10.1126/sciadv.aay9789. View

Lan G, Ni K, Veroneau S, Luo T, You E, Lin W . Nanoscale Metal-Organic Framework Hierarchically Combines High-Z Components for Multifarious Radio-Enhancement. J Am Chem Soc. 2019; 141(17):6859-6863. DOI: 10.1021/jacs.9b03029. View

Xu Z, Ni K, Mao J, Luo T, Lin W . Monte Carlo Simulations Reveal New Design Principles for Efficient Nanoradiosensitizers Based on Nanoscale Metal-Organic Frameworks. Adv Mater. 2021; 33(40):e2104249. PMC: 8492529. DOI: 10.1002/adma.202104249. View

Ding Z, Guo Z, Zheng Y, Wang Z, Fu Q, Liu Z . Radiotherapy Reduces -Oxides for Prodrug Activation in Tumors. J Am Chem Soc. 2022; 144(21):9458-9464. DOI: 10.1021/jacs.2c02521. View

Manna K, Ji P, Greene F, Lin W . Metal-Organic Framework Nodes Support Single-Site Magnesium-Alkyl Catalysts for Hydroboration and Hydroamination Reactions. J Am Chem Soc. 2016; 138(24):7488-91. DOI: 10.1021/jacs.6b03689. View

Zhou C, Hao G, Thomas P, Liu J, Yu M, Sun S . Near-infrared emitting radioactive gold nanoparticles with molecular pharmacokinetics. Angew Chem Int Ed Engl. 2012; 51(40):10118-22. DOI: 10.1002/anie.201203031. View

Overchuk M, Cheng M, Zheng G . X-ray-Activatable Photodynamic Nanoconstructs. ACS Cent Sci. 2020; 6(5):613-615. PMC: 7256960. DOI: 10.1021/acscentsci.0c00303. View

10.

Lu K, He C, Guo N, Chan C, Ni K, Lan G . Low-dose X-ray radiotherapy-radiodynamic therapy via nanoscale metal-organic frameworks enhances checkpoint blockade immunotherapy. Nat Biomed Eng. 2019; 2(8):600-610. DOI: 10.1038/s41551-018-0203-4. View

11.

Guo N, Ni K, Luo T, Lan G, Arina A, Xu Z . Reprogramming of Neutrophils as Non-canonical Antigen Presenting Cells by Radiotherapy-Radiodynamic Therapy to Facilitate Immune-Mediated Tumor Regression. ACS Nano. 2021; 15(11):17515-17527. DOI: 10.1021/acsnano.1c04363. View

12.

Lan G, Ni K, Veroneau S, Song Y, Lin W . Nanoscale Metal-Organic Layers for Radiotherapy-Radiodynamic Therapy. J Am Chem Soc. 2018; 140(49):16971-16975. DOI: 10.1021/jacs.8b11593. View

13.

Gong L, Zhang Y, Liu C, Zhang M, Han S . Application of Radiosensitizers in Cancer Radiotherapy. Int J Nanomedicine. 2021; 16:1083-1102. PMC: 7886779. DOI: 10.2147/IJN.S290438. View

14.

Sun Y, Feng X, Wan C, Lovell J, Jin H, Ding J . Role of nanoparticle-mediated immunogenic cell death in cancer immunotherapy. Asian J Pharm Sci. 2021; 16(2):129-132. PMC: 8105413. DOI: 10.1016/j.ajps.2020.05.004. View

15.

Schaue D, McBride W . Opportunities and challenges of radiotherapy for treating cancer. Nat Rev Clin Oncol. 2015; 12(9):527-40. PMC: 8396062. DOI: 10.1038/nrclinonc.2015.120. View

16.

Delaney G, Barton M . Evidence-based estimates of the demand for radiotherapy. Clin Oncol (R Coll Radiol). 2014; 27(2):70-6. DOI: 10.1016/j.clon.2014.10.005. View

17.

Kong H, Chandel N . Regulation of redox balance in cancer and T cells. J Biol Chem. 2017; 293(20):7499-7507. PMC: 5961053. DOI: 10.1074/jbc.TM117.000257. View

18.

Jiang X, Du B, Yu M, Jia X, Zheng J . Surface-ligand effect on radiosensitization of ultrasmall luminescent gold nanoparticles. J Innov Opt Health Sci. 2017; 9(4):16420031-16420038. PMC: 5639719. DOI: 10.1142/S1793545816420037. View

19.

Suda Y, Hariu M, Yamauchi R, Miyasaka R, Myojoyama A, Chang W . Direct energy spectrum measurement of X-ray from a clinical linac. J Appl Clin Med Phys. 2021; 22(8):255-264. PMC: 8364277. DOI: 10.1002/acm2.13354. View

20.

Wang C, Volotskova O, Lu K, Ahmad M, Sun C, Xing L . Synergistic assembly of heavy metal clusters and luminescent organic bridging ligands in metal-organic frameworks for highly efficient X-ray scintillation. J Am Chem Soc. 2014; 136(17):6171-4. PMC: 4017603. DOI: 10.1021/ja500671h. View