Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy
Advanced multimodal nanoparticles delay tumor progression with clinical radiation therapy
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DOI：
10.1016/j.jconrel.2016.07.021
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发表时间：
2016-09-28
影响因子：
10.8
通讯作者：
Berbeco, Ross
中科院分区：
文献类型：
--
作者：
Detappe, Alexandre;Kunjachan, Sijumon;Berbeco, Ross
放射治疗是超过50%的癌症患者的主要治疗方案。在辐射期间对健康组织诱导的附带损伤和对感兴趣的器官（靶）的最小治疗效果是主要的临床问题。超小型、肾脏可清除的二氧化硅基钆螯合纳米颗粒（SiGdNP）可同时增强MR对比度和辐射剂量。钆的高原子序数为增加的光子相互作用提供了大的光电横截面，即使对于高能临床辐射束也是如此。SiGdNP的成像和治疗功能分别在食蟹猴和携带胰腺肿瘤的小鼠模型中测试。在人胰腺异种移植模型中观察到临床放射治疗条件下肿瘤细胞损伤（双链DNA断裂）、生长抑制和总生存期的显著改善。首次在两种试验种属中证明了安全的全身给药和全身肾脏清除率。这些发现强烈支持SiGdNP在癌症治疗中用于MR引导的放射疗法的转化潜力。(C)2016爱思唯尔B.V.保留所有权利。
Radiation therapy is a major treatment regimen for more than 50% of cancer patients. The collateral damage induced on healthy tissues during radiation and the minimal therapeutic effect on the organ-of-interest (target) is a major clinical concern. Ultra-small, renal clearable, silica based gadolinium chelated nanoparticles (SiGdNP) provide simultaneous MR contrast and radiation dose enhancement. The high atomic number of gadolinium provides a large photoelectric cross-section for increased photon interaction, even for high-energy clinical radiation beams. Imaging and therapy functionality of SiGdNP were tested in cynomolgus monkeys and pancreatic tumor-bearing mice models, respectively. A significant improvement in tumor cell damage (double strand DNA breaks), growth suppression, and overall survival under clinical radiation therapy conditions were observed in a human pancreatic xenograft model. For the first time, safe systemic administration and systematic renal clearance was demonstrated in both tested species. These findings strongly support the translational potential of SiGdNP for MR-guided radiation therapy in cancer treatment. (C) 2016 Elsevier B.V. All rights reserved.