Hyaluronic acid-ceramide-based optical/MR dual imaging nanoprobe for cancer diagnosis

Hyaluronic acid-ceramide-based optical/MR dual imaging nanoprobe for cancer diagnosis
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DOI:
10.1016/j.jconrel.2012.06.011
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发表时间:
2012-08-20
影响因子:
10.8
通讯作者:
Kim, Dae-Duk
Kim, Dae-Duk
中科院分区:
医学1区
文献类型:
--
作者:
Cho, Hyun-Jong;Yoon, Hong Yeol;Kim, Dae-Duk

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开发了用于磁共振(MR)和光学成像的基于羟乙磺酸-神经酰胺(HACE)的纳米探针,用于癌症诊断。将二乙烯三胺五乙酸二酐(DTPA)与HACE结合,用于螯合钆(Gd)作为MR造影剂。Cy5.5也作为近红外荧光(NIRF)成像染料与HACE骨架缀合。自组装的基于HACE-DTPA-Gd的纳米探针Cy 5. 5-HACE-DTPA-Gd表现出均匀分布的粒径和形态形状。在U87-MG(CD 44受体低表达)和SCC 7(CD 44受体高表达)细胞中,基于HACE的纳米探针未诱导严重的细胞毒性。在SCC 7细胞中,基于HEC的纳米探针的细胞摄取效率高于U87-MG细胞,表明HA-CD 44受体相互作用。与商业制剂(Magnevist)相比,证实了基于HACE的纳米探针的体外MR信号增强。此外,在SCC 7肿瘤异种移植小鼠模型中验证了肿瘤区域中基于HACE的纳米探针的体内MR对比度增强。通过NIRF成像研究监测所开发的纳米探针的肿瘤靶向能力,并观察到纳米探针在肿瘤区域中的积累改善。因此,这种基于HACE的双重成像纳米探针可用于基于其被动和主动肿瘤靶向策略对癌症进行更准确的诊断。(C)2012年爱思唯尔B。V.保留所有权利。
Hyaluronic acid-ceramide (HACE)-based nanoprobes for magnetic resonance (MR) and optical imaging were developed for cancer diagnosis. Diethylenetriaminepentaacetic dianhydride (DTPA) was conjugated to HACE for the chelation of gadolinium (Gd) as an MR contrast agent. Cy5.5 was also conjugated to the HACE backbone as a near-infrared fluorescence (NIRF) imaging dye. The self-assembled HACE-based nanoprobe, Cy5.5-HACE-DTPA-Gd, exhibited a uniformly distributed particle size and morphological shape. The HACE-based nanoprobe did not induce serious cytotoxicity in U87-MG (low expression of CD44 receptor) and SCC7 (high expression of CD44 receptor) cells. The cellular uptake efficiency of the HACE-based nanoprobe was higher in SCC7 cells than in U87-MG cells, indicating an HA-CD44 receptor interaction. In vitro MR signal enhancement of the HACE-based nanoprobe was confirmed compared with a commercial formulation (Magnevist). Moreover, in vivo MR contrast enhancement of the HACE-based nanoprobe in the tumor region was verified in an SCC7 tumor xenograft mouse model. The tumor targetability of the developed nanoprobe was monitored by an NIRF imaging study, and improved accumulation of the nanoprobe in the tumor region was observed. Therefore, this HACE-based dual-imaging nanoprobe can be used to make a more accurate diagnosis of cancer based on its passive and active tumor targeting strategies. (C) 2012 Elsevier B. V. All rights reserved.