Department of Chemistry, The University of Chicago, Chicago, IL-60637, USA.
Department of Radiation and Cellular Oncology and Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL-60637, USA.
Angew Chem Int Ed Engl. 2022 Nov 14;61(46):e202208685. doi: 10.1002/anie.202208685. Epub 2022 Oct 17.
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.
基于高 Z 金属的纳米级金属有机骨架(nMOFs)与光敏配体结合,可以通过独特的放射治疗-放射动力学治疗(RT-RDT)过程增强肿瘤的放射损伤。在这里,我们报告了基于 Th-氧次构筑单元和 5,15-二(对苯甲酰基)卟啉(DBP)配体构建的 Th 基 nMOF 的蒙特卡罗(MC)模拟指导设计,用于增强 RT-RDT。MC 模拟表明,由于 Th 晶格的质量衰减系数较高,其在辐射剂量增强方面优于 Hf 晶格。在 X 射线或 γ 射线辐射下,Th-DBP 增强了能量沉积,产生了更多的活性氧物质,并对癌细胞的细胞毒性明显高于先前报道的 Hf-DBP nMOF。在低剂量 X 射线照射下,Th-DBP 在结肠癌和胰腺癌小鼠模型中分别抑制了 88%和 97%的肿瘤生长。