AI Article Synopsis
- Heavy-metal-based nanoscale metal-organic frameworks (nMOFs) are proposed as effective radiosensitizers for radiotherapy by generating reactive oxygen species (ROS) that enhance energy deposition during treatment.
- A novel nMOF, Hf-TP-SN, has been designed with an X-ray-triggerable prodrug (SN38) for combined radiotherapy and chemotherapy, aiming to release drugs on-demand when exposed to X-ray irradiation.
- The results show that Hf-TP-SN significantly increases the release of SN38, leading to greater cytotoxicity against cancer cells and effectively inhibiting tumor growth in models of colon and breast cancer.
Article Abstract
As heavy-metal-based nanoscale metal-organic frameworks (nMOFs) are excellent radiosensitizers for radiotherapy via enhanced energy deposition and reactive oxygen species (ROS) generation, we hypothesize that nMOFs with covalently conjugated and X-ray triggerable prodrugs can harness the ROS for on-demand release of chemotherapeutics for chemoradiotherapy. Herein, we report the design of a novel nMOF, Hf-TP-SN, with an X-ray-triggerable 7-ethyl-10-hydroxycamptothecin (SN38) prodrug for synergistic radiotherapy and chemotherapy. Upon X-ray irradiation, electron-dense Hf secondary building units serve as radiosensitizers to enhance hydroxyl radical generation for the triggered release of SN38 via hydroxylation of the 3,5-dimethoxylbenzyl carbonate followed by 1,4-elimination, leading to 5-fold higher release of SN38 from Hf-TP-SN than its molecular counterpart. As a result, Hf-TP-SN plus radiation induces significant cytotoxicity to cancer cells and efficiently inhibits tumor growth in colon and breast cancer mouse models.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472429 | PMC |
| http://dx.doi.org/10.1021/jacs.3c04602 | DOI Listing |
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