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一种用于双模式分子成像的特定肿瘤靶向磁荧光纳米探针。

A specific tumor-targeting magnetofluorescent nanoprobe for dual-modality molecular imaging.

机构信息

Faculty of Medicinal & Applied Chemistry, School of Life Science, Kaohsiung Medical University, Kaohsiung City 80708, Taiwan.

出版信息

Biomaterials. 2010 Mar;31(7):1707-15. doi: 10.1016/j.biomaterials.2009.11.026. Epub 2009 Dec 6.

Abstract

Poly(acrylic acid) was decorated onto Fe(3)O(4) resulting in a highly water-soluble superparamagnetic iron oxide. The Poly(acrylic acid) iron oxide (PAAIO) complexes possess specific magnetic properties in the presence of an external magnetic field and are attractive contrast agents for magnetic resonance imaging (MRI). The free carboxylic groups of PAAIO exposed on the surface allow for covalent attachment of a fluorescent dye, Rhodamine 123 (Rh123) to form PAAIO-Rh123, which permits applications in fluorescence imaging. PAAIO-Rh123 is therefore a dual-modality molecular probe. In order to endow specific properties to compounds that target cancer cells and to prevent recognition by the reticuloendothelial system (RES), folic acid-linked poly(ethylene glycol) (FA-PEG) was further conjugated onto PAAIO-Rh123. The amounts of Rh123 and FA-PEG on the modified iron oxides were quantitatively determined by elemental analysis. The iron content was determined by inductively coupled plasma-optical emission spectrometer (ICP-OES). The particle diameters were characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). Superparamagnetism was confirmed by the superconducting quantum interference device (SQUID) magnetometer. The cellular internalization efficacy of the modified iron oxides was realized in folate-overexpressed FR(+) and folate-deficient FR(-) KB cells by flow cytometry and confocal laser scanning microscopy (CLSM). The quantitative amount of iron internalized into different harvested KB cells was measured by ICP-OES. The T(2)-weighted MR images were tested in FR(+) KB cells.

摘要

聚丙烯酸被修饰到 Fe3O4 上,得到了一种高水溶性的超顺磁性氧化铁。聚(丙烯酸)铁氧化物(PAAIO)复合物在外磁场存在下具有特定的磁性,并且是磁共振成像(MRI)的有吸引力的对比剂。PAAIO 表面暴露的游离羧酸基团允许共价连接荧光染料 Rhodamine 123(Rh123),形成 PAAIO-Rh123,这允许在荧光成像中应用。因此,PAAIO-Rh123 是一种双模态分子探针。为了赋予靶向癌细胞的化合物特定的性质并防止被网状内皮系统(RES)识别,进一步将叶酸连接的聚乙二醇(FA-PEG)共轭到 PAAIO-Rh123 上。通过元素分析定量确定修饰的氧化铁上 Rh123 和 FA-PEG 的量。通过电感耦合等离子体 - 光学发射光谱仪(ICP-OES)确定铁含量。通过动态光散射(DLS)和透射电子显微镜(TEM)对粒径进行了表征。超顺磁性通过超导量子干涉器件(SQUID)磁力计得到证实。通过流式细胞术和共聚焦激光扫描显微镜(CLSM)在叶酸过表达 FR(+)和叶酸缺乏 FR(-)KB 细胞中实现了修饰的氧化铁的细胞内化效力。通过 ICP-OES 测量不同收获的 KB 细胞内化的铁的定量量。在 FR(+)KB 细胞中测试了 T2 加权磁共振图像。

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