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首页> 外文期刊>Clinical and investigative medicine: Medecine clinique et experimentale >The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model
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The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model

机译：胆碱结合的金纳米粒子在人前列腺肿瘤异种移植模型中的生物分布和药代动力学评估

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Purpose: Gold nanoparticles (GNPs) have attracted signiffcant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. The aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI). Methods: Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Toxicity of choline-GNPs was examined on DU-145 prostate cancer cells using an MTT assay. Using balb/c mice bearing flank DU-145 prostate tumors, choline-GNPs bio-distribution was measured using inductively coupled mass spectroscopy (ICP-MS). Blood, heart, lung, liver, spleen, brain, kidney and tumor gold content were examined at multiple time points over a 24-hour period after tail vein injection. Results: An MTT assay using DU-145 prostate cancer cells yielded a 95% cell viability 72 hours after choline-GNP administration. The tumor GNP area under the concentrationtime curve during the first 4 hours (AUC0-4) was 2.2 μg/ml h, representing 13% of the circulating blood GNP concentration over the same time period. The maximum intratumor GNP concentration observed was 1.4% of the injected dose per gram of tumor tissue (%ID/g) one hour post injection. Conclusions: GNPs functionalized with choline demonstrates a viable future nanoparticle platform with increased intra-tumor uptake as compared to unconjugated GNPs. Decreased intra-hepatic accumulation appears to be the reason for the improved systemic bioavailability.The next logical translational investigation will incorporate external beam radiation with the observed maximum intra-tumor uptake.
机译：目的：金纳米颗粒（GNP）由于其作为新型放射增强剂的潜力而在癌症治疗中引起了极大的关注，尤其是在被各种靶向配体官能化时。这项研究的目的是评估用聚乙烯亚胺（PEI）稳定的新型胆碱结合的GNP（胆碱-GNP）的生物分布和药代动力学特征。方法：使用透射电子显微镜（TEM），X射线光电子能谱（XPS）和傅里叶变换红外光谱（FTIR）表征与27 nm直径GNP结合的胆碱。使用MTT测定法在DU-145前列腺癌细胞上检查了胆碱-GNP的毒性。使用携带侧面DU-145前列腺肿瘤的balb / c小鼠，使用电感耦合质谱法（ICP-MS）测量胆碱GNP的生物分布。尾静脉注射后24小时内在多个时间点检查血液，心脏，肺，肝，脾，脑，肾和肿瘤的含金量。结果：在使用胆碱-GNP 72小时后，使用DU-145前列腺癌细胞的MTT分析得出了95％的细胞活力。在最初的4小时内（AUC0-4）在浓缩时间曲线下的肿瘤GNP面积为2.2μg/ ml h，占同期血液循环GNP浓度的13％。注射后一小时观察到的最大肿瘤内GNP浓度为每克肿瘤组织注射剂量的1.4％（％ID / g）。结论：用胆碱官能化的GNPs证明了与未结合的GNPs相比，未来可行的纳米颗粒平台具有更高的肿瘤吸收率。肝内积累减少似乎是全身生物利用度提高的原因。下一个逻辑平移研究将结合外部束辐射，观察到最大的肿瘤内吸收。

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