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金纳米粒子在肿瘤中的优先积累通过磁共振成像可视化:体内和体外的放射增敏研究。

Preferential tumour accumulation of gold nanoparticles, visualised by Magnetic Resonance Imaging: radiosensitisation studies in vivo and in vitro.

机构信息

Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Quebec, Canada.

出版信息

Int J Radiat Biol. 2010 Aug;86(8):692-700. doi: 10.3109/09553001003746067.

Abstract

PURPOSE

To investigate the radiosensitisation of gold nanoparticles (GNP) with an average diameter of 5 nm coated with the gadolinium chelating agent dithiolated diethylenetriaminepentaacetic gadolinium (Au@DTDTPA:Gd) in vitro and in mice bearing tumours (MC7-L1).

MATERIALS AND METHODS

In vivo, the gadolinium chelate coating allows one to perform real-time Magnetic Resonance Imaging (MRI) pharmacokinetic analysis during intravenous infusion. Experiments were performed following treatment with 10 Gy of 150 kVp X-rays. In vitro experiments were also performed with clonogenic assays to generate dose response curves for the same cells.

RESULTS

We observed a preferential accumulation of Au@DTDTPA:Gd in tumours; a substantial toxicity for tumour cells in vitro, but no obvious toxicity for mice; and the absence of a synergistic effect with Au@DTDTPA:Gd and radiation in all experiments.

CONCLUSIONS

The additional absorption of radiation and the subsequent increase in secondary electrons, attributable to the presence of gold in Au@DTDTPA:Gd, does not lead to radiosensitisation. However, this chelating agent exhibits a chemotherapeutic action which warrants further investigation. When compared to positive results obtained by others on radiosensitisation by GNP, the present study suggests that the chemotherapeutic and radiosensitising properties of GNP may depend strongly on the nature of the coating.

摘要

目的

研究平均直径为 5nm 的金纳米粒子(GNP)的增敏作用,这些 GNP 表面涂有钆螯合剂二硫代二乙三胺五乙酸(Au@DTDTPA:Gd),在体外和荷瘤(MC7-L1)小鼠中进行。

材料和方法

在体内,通过静脉注射时,使用该钆螯合物涂层可以进行实时磁共振成像(MRI)药代动力学分析。在 150kVp X 射线照射 10Gy 后进行实验。还进行了体外实验,通过集落形成试验为相同细胞生成剂量反应曲线。

结果

我们观察到 Au@DTDTPA:Gd 在肿瘤中有优先积累;体外对肿瘤细胞有明显毒性,但对小鼠无明显毒性;并且在所有实验中,Au@DTDTPA:Gd 与辐射之间没有协同作用。

结论

由于 Au@DTDTPA:Gd 中存在金,导致额外吸收辐射和随后增加二次电子,但这并没有导致增敏作用。然而,这种螯合剂表现出化学治疗作用,值得进一步研究。与其他人关于 GNP 增敏作用的阳性结果相比,本研究表明 GNP 的化学治疗和增敏作用可能强烈依赖于涂层的性质。

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