Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Lyon-1 University, Institut Lumière Matière, CNRS UMR5306, Lyon, France.
Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
J Control Release. 2016 Sep 28;238:103-113. doi: 10.1016/j.jconrel.2016.07.021. Epub 2016 Jul 14.
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.
放射疗法是 50%以上癌症患者的主要治疗方案。在放射治疗过程中对健康组织造成的附带损害以及对靶器官（目标）的最小治疗效果是一个主要的临床关注点。超小、可经肾脏清除的、基于硅的钆螯合物纳米颗粒（SiGdNP）提供了同时的磁共振对比增强和辐射剂量增强。钆的高原子序数为增加光子相互作用提供了一个大的光电截面，即使是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胰腺癌荷瘤小鼠模型中进行了测试。在人胰腺异种移植模型中，在临床放射治疗条件下观察到肿瘤细胞损伤（双链 DNA 断裂）、生长抑制和整体存活率的显著改善。首次在两种受试物种中证明了安全的全身给药和系统的肾脏清除。这些发现有力地支持了 SiGdNP 在癌症治疗中用于磁共振引导放射治疗的转化潜力。
