Nanomedicine recently emerged as a novel strategy to improve the performance of radiotherapy. Herein we report the first application of radioenhancers made of nanoscale metal-organic frameworks (nanoMOFs), loaded with gemcitabine monophosphate (Gem-MP), a radiosensitizing anticancer drug. Iron trimesate nanoMOFs possess a regular porous structure with oxocentered Fe trimers separated by around 5 Å (trimesate linkers). This porosity is favorable to diffuse the electrons emitted from nanoMOFs due to activation by γ radiation, leading to water radiolysis and generation of hydroxyl radicals which create nanoscale damages in cancer cells. Moreover, nanoMOFs act as "Trojan horses", carrying their Gem-MP cargo inside cancer cells to interfere with DNA repair. By displaying different mechanisms of action, both nanoMOFs and incorporated Gem-MP contribute to improve radiation efficacy. The radiation enhancement factor of Gem-MP loaded nanoMOFs reaches 1.8, one of the highest values ever reported. These results pave the way toward the design of engineered nanoparticles in which each component plays a role in cancer treatment by radiotherapy.

中文翻译：

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载有吉西他滨单磷酸酯的高度多孔的杂化金属有机纳米颗粒：改善化学疗法和放射疗法的多峰方法。

纳米医学最近作为一种改善放射治疗性能的新策略而出现。本文中，我们报道了由纳米级金属-有机骨架（nanoMOF）制成的放射性增强剂的首次应用，纳米级金属有机骨架负载了吉西他滨单磷酸酯（Gem-MP），这是一种放射增敏的抗癌药物。偏苯三酸铁纳米MOF具有规则的多孔结构，其以氧中心的铁三聚体相隔约5Å（三酸酯连接体）。这种孔隙率有利于扩散由于被γ射线激活而从nanoMOF发出的电子，从而导致水辐射分解和羟基自由基的产生，从而在癌细胞中产生纳米级损伤。此外，nanoMOF充当“特洛伊木马”，将其Gem-MP货物携带在癌细胞内，以干扰DNA修复。通过展示不同的作用机制，nanoMOF和掺入的Gem-MP均有助于提高放射功效。载有Gem-MP的nanoMOF的辐射增强因子达到1.8，这是有史以来的最高值之​​一。这些结果为工程纳米颗粒的设计铺平了道路，其中每种成分在通过放射疗法治疗癌症中都发挥着作用。