Department of Radiology, University of Missouri, Columbia, Missouri 65211, USA.
Nanomedicine. 2010 Apr;6(2):201-9. doi: 10.1016/j.nano.2009.11.001. Epub 2009 Nov 12.
Biocompatibility studies and cancer therapeutic applications of nanoparticulate beta-emitting gold-198 (198Au; beta(max) = 0.96 MeV; half-life of 2.7 days) are described. Gum arabic glycoprotein (GA)-functionalized gold nanoparticles (AuNPs) possess optimum sizes (12-18 nm core diameter and 85 nm hydrodynamic diameter) to target individual tumor cells and penetrate through tumor vasculature and pores. We report the results of detailed in vivo therapeutic investigations demonstrating the high tumor affinity of GA-198AuNPs in severely compromised immunodeficient (SCID) mice bearing human prostate tumor xenografts. Intratumoral administration of a single dose of beta-emitting GA-198AuNPs (70 Gy) resulted in clinically significant tumor regression and effective control in the growth of prostate tumors over 30 days. Three weeks after administration of GA-198AuNPs, tumor volumes for the treated animals were 82% smaller as compared with tumor volume of control group. The treatment group showed only transitory weight loss in sharp contrast to the tumor-bearing control group, which underwent substantial weight loss. Pharmacokinetic studies have provided unequivocal evidence for the optimum retention of therapeutic payload of GA-198AuNPs within the tumor site throughout the treatment regimen with minimal or no leakage of radioactivity to various nontarget organs. The measurements of white and red blood cells, platelets, and lymphocytes within the treatment group resembled those of the normal SCID mice, thus providing further evidence on the therapeutic efficacy and concomitant in vivo tolerance and nontoxic features of GA-198AuNPs.
In this study, the biocompatibility and cancer therapeutic applications of glycoprotein (GA) functionalized gold nanoparticles containing b-emitting Au-198 are described in SCID mice bearing human prostate tumor xenografts. The findings of significant therapeutic efficacy, good in vivo tolerance and non-toxic features make these particles ideal candidates for future human applications.
本文描述了纳米放射性金-198（198Au；β最大=0.96 MeV；半衰期为 2.7 天）的生物相容性研究和癌症治疗应用。阿拉伯树胶糖蛋白（GA）功能化的金纳米粒子（AuNPs）具有最佳的尺寸（12-18nm 核直径和 85nm 水动力直径），可以靶向单个肿瘤细胞并穿透肿瘤血管和孔隙。我们报告了详细的体内治疗研究结果，这些结果表明，GA-198AuNPs 在严重免疫缺陷（SCID）小鼠携带人前列腺肿瘤异种移植物中具有很高的肿瘤亲和力。单次给予β放射性 GA-198AuNPs（70Gy）可导致肿瘤明显消退，并在 30 天内有效控制前列腺肿瘤生长。给予 GA-198AuNPs 3 周后，与对照组相比，治疗组的肿瘤体积缩小了 82%。与肿瘤对照组相比，治疗组仅出现短暂性体重减轻，而肿瘤对照组体重明显减轻。药代动力学研究提供了确凿的证据，证明在整个治疗过程中，GA-198AuNPs 的治疗有效载荷在肿瘤部位得到了最佳保留，放射性核素很少或没有漏到各种非靶器官。治疗组的白细胞、红细胞、血小板和淋巴细胞的测量值与正常 SCID 小鼠相似，这进一步证明了 GA-198AuNPs 的治疗效果以及体内耐受性和无毒特性。
在这项研究中，在携带人前列腺肿瘤异种移植物的 SCID 小鼠中，描述了含有β放射性 Au-198 的糖蛋白（GA）功能化金纳米粒子的生物相容性和癌症治疗应用。这些粒子具有显著的治疗效果、良好的体内耐受性和无毒特性，使其成为未来人类应用的理想候选物。
