Jasim Dhifaf A, Ménard-Moyon Cécilia, Bégin Dominique, Bianco Alberto, Kostarelos Kostas
Nanomedicine Laboratory , Faculty of Medical & Human Sciences and National Graphene Institute , University of Manchester , AV Hill Building , Manchester M13 9PT , UK . Email:
CNRS , Institut de Biologie Moléculaire et Cellulaire , Laboratoire d'Immunopathologie et Chimie Thérapeutique , 67000 Strasbourg , France . Email:
Chem Sci. 2015 Jul 15;6(7):3952-3964. doi: 10.1039/c5sc00114e. Epub 2015 Apr 14.
The design of graphene-based materials for biomedical purposes is of great interest. Graphene oxide (GO) sheets represent the most widespread type of graphene materials in biological investigations. In this work, thin GO sheets were synthesized and further chemically functionalized with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), a stable radiometal chelating agent, by an epoxide opening reaction. We report the tissue distribution of the functionalized GO sheets labeled with radioactive indium (In) after intravenous administration in mice. Whole body single photon emission computed tomography (SPECT/CT) imaging, gamma counting studies, Raman microscopy and histological investigations indicated extensive urinary excretion and predominantly spleen accumulation. Intact GO sheets were detected in the urine of injected mice by Raman spectroscopy, high resolution transmission electron microscopy (HR-TEM) and electron diffraction. These results offer a previously unavailable pharmacological understanding on how chemically functionalized GO sheets transport in the blood stream and interact with physiological barriers that will determine their body excretion and tissue accumulation.
用于生物医学目的的基于石墨烯的材料设计备受关注。氧化石墨烯（GO）片是生物研究中最广泛使用的石墨烯材料类型。在这项工作中，通过开环反应合成了薄的GO片，并进一步用稳定的放射性金属螯合剂DOTA（1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸）进行化学功能化。我们报告了在小鼠静脉注射后，用放射性铟（In）标记的功能化GO片的组织分布情况。全身单光子发射计算机断层扫描（SPECT/CT）成像、γ计数研究、拉曼显微镜和组织学研究表明，其大量经尿液排泄，主要蓄积在脾脏。通过拉曼光谱、高分辨率透射电子显微镜（HR-TEM）和电子衍射在注射小鼠的尿液中检测到完整的GO片。这些结果为化学功能化的GO片在血流中的运输方式以及与决定其体内排泄和组织蓄积的生理屏障的相互作用提供了前所未有的药理学认识。
