摘要/Abstract
基于金纳米簇强烈的量子限制效应(strong quantum confinement effect,SQCE),采用一步合成法,制备了同时具有高效近红外荧光与CT双模态成像能力的超小金纳米簇.实验表明,通过优化合成比例以及合成条件,所合成的超小金纳米簇具有很大的斯托克斯(Stokes)位移、较高的荧光强度和X射线吸收效率.除此之外,该超小金纳米簇具有良好的单分散性、稳定性和生物相容性.4T1肿瘤细胞荧光成像实验结果表明,该纳米粒子可被肿瘤细胞快速、高效地摄取.
关键词: 超小金纳米簇, 荧光成像, CT成像, 双模态成像
Multimodality imaging can integrate structural/functional information from different imaging tools, thus provide more accurate diagnosis than each single imaging modality. Au nanoclusters (AuNCs) are unique and have rich X-ray attenuation and fluorescent properties based on strong quantum confinement effect (SQCE); however, there is a huge challenge to simultaneously improve both X-ray imaging ability and fluorescent properties by adjusting sizes under the requirements of in vivo biological application. In this study, using rGSH as reductant and stabilizer, we developed a sub-nanometer ultrasmall AuNCs (Us-Au15NCs) as an optimized multimodal imaging probe with enhanced imaging ability by accurately adjusting pH to 8. For the first time, the in vitro both enhanced fluorescent and X-ray computed tomography (CT) bimodal imaging ability of AuNCs were investigated. By adjusting the pH and the proportion of Au3+ ions to GSH, the fluorescence intensity of the Us-AuNCs was strengthened and the emission peak showed red-shifts from 510 nm to 683 nm. While promising and exciting, the attenuation coefficient verified by the HU (hounsfield unit) values was increased almost linearly with the ratio increasing, which preserved the excellent X-ray imaging ability of Us-AuNCs. In addition, With a demonstrated better X-ray attenuation property than that of clinically used iodinated small molecular contrast agent (e.g., Iohexol), the developed Us-Au15NCs enabled efficient and enhanced CT imaging. Thus, the synthesized Us-Au15NCs characterised by UV-vis spectra and fluorescence spectra could simultaneously possess superior CT contrast ability and significant photoluminescence properties. Transmission electron microscopy (TEM) results revealed that the morphology was uniform spherical shape. Moreover, the Us-Au15NCs shows excellent stability, low cytotoxicity and good biocompatibility. Furthermore, the prepared Us-Au15NCs was confirmed to be effective and applicable for fluorescent imaging of 4T1 tumor cells, which determining that the Us-Au15NCs was more effectively involved with the cancer cells. The significance of this study is that rather than the synthesis of Us-AuNCs only, the prepared Us-Au15NCs may serve as multimodality imaging contrast agent with fluorescence and CT imaging for clinical diagnosis application.
Key words: ultrasmall AuNCs, fluorescence imaging, CT imaging, bimodal imaging
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