Establishment of a Trimodality Analytical Platform for Tracing, Imaging and Quantification of Gold Nanoparticles in Animals by Radiotracer Techniques

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• 作者：Chien-Hung Chen ; Fong-Sian Lin ; Wei-Neng Liao ; Sanching L. Liang ; Min-Hua Chen ; Yo-Wen Chen ; Wan-Yu Lin ; Ming-Hua Hsu ; Mei-Ya Wang ; Jinn-Jer Peir ; Fong-In Chou ; Ching-Ya Chen ; Sih-Yu Chen ; Su-Chin Huang ; Mo-Hsiung Yang ; Dueng-Yuan Hueng ; Yeukuang Hwu ; Chung-Shi Yang ; Jen-Kun Chen
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：January 6, 2015
• 年：2015
• 卷：87
• 期：1
• 页码：601-608
• 全文大小：365K
• ISSN：1520-6882

文摘

This study aims to establish a ¹⁹⁸Au-radiotracer technique for in vivo tracing, rapid quantification, and ex vivo visualization of PEGylated gold nanoparticles (GNPs) in animals, organs and tissue dissections. The advantages of GNPs lie in its superior optical property, biocompatibility and versatile conjugation chemistry, which are promising to develop diagnostic probes and drug delivery systems. ¹⁹⁸Au is used as a radiotracer because it simultaneously emits beta and gamma radiations with proper energy and half-life; therefore, ¹⁹⁸Au can be used for bioanalytical purposes. The ¹⁹⁸Au-tagged radioactive gold nanoparticles (¹⁹⁸Au-GNPs) were prepared simply by irradiating the GNPs in a nuclear reactor through the ¹⁹⁷Au(n,纬)¹⁹⁸Au reaction and subsequently the ¹⁹⁸Au-GNPs were subjected to surface modification with polyethylene glycol to form PEGylated ¹⁹⁸Au-GNPs. The ¹⁹⁸Au-GNPs retained physicochemical properties that were the same as those of GNP before neutron irradiation. Pharmacokinetic and biodisposition studies were performed by intravenously injecting three types of ¹⁹⁸Au-GNPs with or without PEGylation into mice; the 纬 radiation in blood specimens and dissected organs was then measured. The ¹⁹⁸Au-radiotracer technique enables rapid quantification freed from tedious sample preparation and shows more than 95% recovery of injected GNPs. Clinical gamma scintigraphy was proved feasible to explore spatial- and temporal-resolved biodisposition of ¹⁹⁸Au-GNPs in living animals. Moreover, autoradiography, which recorded beta particles from ¹⁹⁸Au, enabled visualizing the heterogeneous biodisposition of ¹⁹⁸Au-GNPs in different microenvironments and tissues. In this study, the ¹⁹⁸Au-radiotracer technique facilitated creating a trimodality analytical platform for tracing, quantifying and imaging GNPs in animals.