pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin for MR and fluorescence imaging of glioma in rats
pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin for MR and fluorescence imaging of glioma in rats
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DOI：
10.1016/j.biomaterials.2013.05.078
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发表时间：
2013-10-01
期刊：
影响因子：
14
通讯作者：
Yang, Xiangliang
中科院分区：
文献类型：
--
作者：
Jiang, Lingyu;Zhou, Qing;Yang, Xiangliang
神经胶质瘤是最常见的原发性脑肿瘤，在广泛的个体中引起不成比例的发病率和死亡率。从以往的临床实践来看，胶质瘤切缘的界定是手术切除的关键。为了更准确地勾画胶质瘤的边缘，为临床医生在术前计划和手术切除阶段提供指导，本研究开发了一种新型的pH/温度敏感的磁性纳米凝胶（Cy 5. 5-Lf-MPNA nanogels），该纳米凝胶结合了Cy 5. 5-Lf-MPNA标记的乳铁蛋白。由于其pH/温度敏感性，Cy5.5-Lf-MPNA纳米凝胶可以在不同pH和温度下改变其亲水/疏水性质和尺寸。在生理条件下（pH7.4，37 ℃），Cy5.5-Lf-MPNA纳米凝胶具有亲水性和溶胀性，可延长血液循环时间。在肿瘤组织的酸性环境中（pH 6.8，37 ℃），Cy5.5-Lf-MPNA纳米凝胶变得疏水并收缩，其可以更容易地在肿瘤组织中积累并被肿瘤细胞内化。此外，乳铁蛋白作为胶质瘤的有效靶向配体，提供了主动的肿瘤靶向能力。对大鼠原位胶质瘤的体内研究表明，由于Lf的主动靶向功能和通过定制纳米凝胶的亲水/疏水特性来增强细胞摄取，使用Cy 5. 5-Lf-MPNA纳米凝胶可以获得具有高灵敏度和特异性的MR/荧光成像。细胞毒性实验和组织病理学分析表明，Cy5.5-Lf-MPNA纳米凝胶具有良好的生物相容性，有望成为胶质瘤术前MRI和术中荧光成像的特异性、高灵敏度造影剂。(C)2013爱思唯尔有限公司保留所有权利。
Glioma is the most common primary brain tumor and causes a disproportionate level of morbidity and mortality across a wide range of individuals. From previous clinical practices, definition of glioma margin is the key point for surgical resection. In order to outline the exact margin of glioma and provide a guide effect for the physicians both at pre-surgical planning stage and surgical resection stage, pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin (Cy5.5-Lf-MPNA nanogels) were developed as a promising contrast agent. Due to its pH/te mperature sensitivity, Cy5.5-Lf-MPNA nanogels could change in its hydrophilic/hydrophobic properties and size at different pH and temperatures. Under physiological conditions (pH 7.4, 37 degrees C), Cy5.5-Lf-MPNA nanogels were hydrophilic and swollen, which could prolong the blood circulation time. In the acidic environment of tumor tissues (pH 6.8, 37 degrees C), Cy5.5-Lf-MPNA nanogels became hydrophobic and shrunken, which could be more easily accumulated in tumor tissue and internalized by tumor cells. In addition, lactoferrin, an effective targeting ligand for glioma, provides active tumor targeting ability. In vivo studies on rats bearing in situ glioma indicated that the MR/fluorescence imaging with high sensitivity and specificity could be acquired using Cy5.5-Lf-MPNA nanogels due to active targeting function of the Lf and enhancement of cellular uptake by tailoring the hydrophilic/hydrophobic properties of the nanogels. With good biocompatibility shown by cytotoxicity assay and histopathological analysis, Cy5.5-Lf-MPNA nanogels are hopeful to be developed as a specific and high-sensitive contrast agent for preoperative MRI and intraoperative fluorescence imaging of glioma. (C) 2013 Elsevier Ltd. All rights reserved.