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X-Ray responsive nanoparticles with triggered release of nitrite, a precursor of reactive nitrogen species, for enhanced cancer radiosensitization
Nanoscale ( IF 5.8 ) Pub Date : 2017-08-31 00:00:00 , DOI: 10.1039/c7nr04684g Fang Liu 1, 2, 3, 4, 5 , Junzhe Lou 2, 3, 4, 5 , Dimitre Hristov 1, 2, 3, 4
Nanoscale ( IF 5.8 ) Pub Date : 2017-08-31 00:00:00 , DOI: 10.1039/c7nr04684g Fang Liu 1, 2, 3, 4, 5 , Junzhe Lou 2, 3, 4, 5 , Dimitre Hristov 1, 2, 3, 4
Affiliation
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Remotely and locally triggered release of therapeutic species by X-ray irradiation is highly desired to enhance the efficacy of radiotherapy. However, the development of such X-ray responsive nanosystems remains a challenge, especially in response to high energy clinically relevant X-ray radiation. Herein, we report novel nitroimidazole ligated gold nanoparticles (AuNPs) that synergistically function to release nitrite, an important precursor for nitric oxide and reactive nitrogen species that sensitize cancer cells, upon radiation with clinically used 6 MeV X-rays, while no release was detected without radiation. These functional AuNPs were prepared with surface-grafted nitroimidazole as the nitrite-releasing agent, cell-penetrating peptide (CPP) to induce nucleus localization, and poly(ethylene glycol) for water solubility. In vitro radiotherapy using such nanoparticles showed enhanced sensitivity of hypoxic cancer cells to X-ray radiation, presumably due to the generation of both reactive oxygen and nitrogen species. The dose modifying factor (DMF) was found to be 0.71 for the dual-functionalized nanoparticle, which indicates that significant lower X-ray doses are required to achieve the same therapeutic effects. Thus, X-ray triggered nitrite release from gold-nitroimidazole nanosystems offers a novel strategy to sensitize cancer cells for improved radiotherapy.
中文翻译：
具有X射线响应能力的纳米颗粒，具有触发释放的亚硝酸盐（一种活性氮物质的前体）的触发作用，可增强癌症的放射敏感性
强烈期望通过X射线辐射来远程和局部触发释放治疗物种，以增强放射疗法的功效。然而，这种对X射线响应的纳米系统的开发仍然是挑战，特别是在对高能量临床相关的X射线辐射的响应中。在此，我们报道了新型的硝基咪唑连接的金纳米颗粒（AuNPs），在临床使用的6 MeV X射线辐射时，具有协同作用，以释放亚硝酸盐（亚硝酸盐和对癌细胞敏感的活性氮物质的重要前体），但未检测到释放没有辐射。这些功能性AuNPs是用表面接枝的硝基咪唑作为亚硝酸盐释放剂，诱导细胞核定位的细胞穿透肽（CPP）和水溶性的聚乙二醇制备的。使用这种纳米粒子的体外放射疗法显示出低氧癌细胞对X射线辐射的敏感性增强，这大概是由于活性氧和氮物种的产生。对于双官能化的纳米颗粒，发现剂量调节因子（DMF）为0.71，这表明需要较低的X射线剂量才能达到相同的治疗效果。因此，X射线触发的亚硝酸盐从金-硝基咪唑纳米系统中释放出来，提供了一种新颖的策略来敏化癌细胞以改善放射治疗。
更新日期：2017-09-22
中文翻译：
具有X射线响应能力的纳米颗粒，具有触发释放的亚硝酸盐（一种活性氮物质的前体）的触发作用，可增强癌症的放射敏感性
强烈期望通过X射线辐射来远程和局部触发释放治疗物种，以增强放射疗法的功效。然而，这种对X射线响应的纳米系统的开发仍然是挑战，特别是在对高能量临床相关的X射线辐射的响应中。在此，我们报道了新型的硝基咪唑连接的金纳米颗粒（AuNPs），在临床使用的6 MeV X射线辐射时，具有协同作用，以释放亚硝酸盐（亚硝酸盐和对癌细胞敏感的活性氮物质的重要前体），但未检测到释放没有辐射。这些功能性AuNPs是用表面接枝的硝基咪唑作为亚硝酸盐释放剂，诱导细胞核定位的细胞穿透肽（CPP）和水溶性的聚乙二醇制备的。使用这种纳米粒子的体外放射疗法显示出低氧癌细胞对X射线辐射的敏感性增强，这大概是由于活性氧和氮物种的产生。对于双官能化的纳米颗粒，发现剂量调节因子（DMF）为0.71，这表明需要较低的X射线剂量才能达到相同的治疗效果。因此，X射线触发的亚硝酸盐从金-硝基咪唑纳米系统中释放出来，提供了一种新颖的策略来敏化癌细胞以改善放射治疗。
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