Khan Mohamed K, Minc Leah D, Nigavekar Shraddha S, Kariapper Muhammed S T, Nair Bindu M, Schipper Matthew, Cook Andrew C, Lesniak Wojciech G, Balogh Lajos P
NanoBiotechnology Center at RPCI, Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.
Nanomedicine. 2008 Mar;4(1):57-69. doi: 10.1016/j.nano.2007.11.005. Epub 2008 Jan 31.
We describe the simple fabrication of poly({198Au}) radioactive gold-dendrimer composite nanodevices in distinct sizes (diameter between 10 nm and 29 nm) for targeted radiopharmaceutical dose delivery to tumors in vivo. Irradiation of aqueous solutions of 197Au containing poly(amidoamine) dendrimer tetrachloroaurate salts or {197Au0} gold-dendrimer nanocomposites in a nuclear reactor resulted in the formation of positively charged and soluble poly{198Au0} radioactive composite nanodevices (CNDs). A mouse melanoma tumor model was used to test whether the poly{198Au0} CNDs can deliver a therapeutic dose. A single intratumoral injection of poly{198Au0}(d=22nm) CNDs in phosphate-buffered saline delivering a dose of 74 muCi resulted after 8 days in a statistically significant 45% reduction in tumor volume, when compared with untreated groups and those injected with the "cold" nanodevice. No clinical toxicity was observed during the experiments. This study provides the first proof of principle that radioactive CNDs can deliver therapeutic doses to tumors.
我们描述了用于体内靶向放射性药物剂量递送至肿瘤的不同尺寸（直径在10纳米至29纳米之间）的聚（{198Au}）放射性金 - 树枝状大分子复合纳米器件的简单制备方法。在核反应堆中对含有聚（酰胺胺）树枝状大分子四氯金酸盐或{197Au0}金 - 树枝状大分子纳米复合材料的197Au水溶液进行辐照，导致形成带正电且可溶的聚{198Au0}放射性复合纳米器件（CND）。使用小鼠黑色素瘤肿瘤模型来测试聚{198Au0} CND是否能递送治疗剂量。在磷酸盐缓冲盐水中单次瘤内注射剂量为74微居里的聚{198Au0}（d = 22纳米）CND，8天后与未治疗组和注射“冷”纳米器件的组相比，肿瘤体积在统计学上显著减少了45％。实验过程中未观察到临床毒性。这项研究提供了首个原理证明，即放射性CND可以向肿瘤递送治疗剂量。
