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首页> 外文期刊>Biomaterials >Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells.
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Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells.

机译:以叶酸受体为靶标的稀土氧化物纳米晶体,用于癌细胞的双峰荧光和磁性成像。

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Targeted cancer imaging using rare-earth oxide nanocrystals, free from heavy metals (Cd, Se, Te, Hg and Pb), showing bright red-fluorescence and magnetic resonance imaging (MRI) is presented. Y(2)O(3) nanocrystals (YO NC) doped in situ with fluorescent (Eu(3+)) and paramagnetic (Gd(3+)) impurities and conjugated with a potential cancer targeting ligand, folic acid (FA), were prepared using an all-aqueous wet-chemical process. Structural, optical and magnetic properties of these multifunctional nanocrystals were investigated by X-ray diffraction, electron microscopy, photoluminescence and magnetization studies. Highly monodisperse nanocrystals of size approximately 20 nm with cubic bixbyite crystal structure showed bright red-fluorescence when doped with Eu(3+). Co-doping with Gd(3+) and mild air drying resulted significantly enhanced fluorescence quantum efficiency of approximately 60% together with paramagnetic functionality, enabling T(1)-weighted MR contrast with approximately 5 times higher spin-lattice relaxivity compared to the clinically used Gd(3+) contrast agent. Cytotoxicity and reactive oxygen stress studies show no toxicity by YO NC in both normal and cancer cells up to higher doses of 500 microm and longer incubation time, 48h. Cancer targeting capability of FA conjugated NCs was demonstrated on folate receptor positive (FR+) human nasopharyngeal carcinoma cells (KB) with FR depressed KB (FRd) and FR negative (FR-) lung cancer cells A549 as controls. Fluorescence microscopy and flow-cytometry data show highly specific binding and cellular uptake of large concentration of FA conjugated NCs on FR+ve cells compared to the controls. Thus, the present study reveals, unique bi-modal contrast imaging capability, non-toxicity and cancer targeting capability of multiple impurities doped rare-earth oxide nanocrystals that can find promising application in molecular imaging.
机译:提出了使用不含重金属(Cd,Se,Te,Hg和Pb)的稀土氧化物纳米晶体的有针对性的癌症成像,显示了亮红色荧光和磁共振成像(MRI)。 Y(2)O(3)纳米晶体(YO NC)原位掺杂荧光(Eu(3+))和顺磁性(Gd(3+))杂质,并与潜在的癌症靶向配体叶酸(FA)结合,用全水湿化学法制备。通过X射线衍射,电子显微镜,光致发光和磁化研究了这些多功能纳米晶体的结构,光学和磁性。当掺杂Eu(3+)时,具有立方方铁锰矿晶体结构的尺寸约为20 nm的高度单分散纳米晶体显示出明亮的红色荧光。与Gd(3+)的共掺杂和温和的空气干燥导致显着提高了约60%的荧光量子效率以及顺磁性功能,从而实现了T(1)加权MR对比,其自旋晶格弛豫性约为临床的5倍使用了Gd(3+)造影剂。细胞毒性和活性氧应激研究表明,YO NC对正常细胞和癌细胞均无毒性,直至500微米的更高剂量和48小时的较长孵育时间。在以FR抑制的KB(FRd)和FR阴性(FR-)肺癌细胞A549作为对照的叶酸受体阳性(FR +)人鼻咽癌细胞(KB)上证实了FA共轭NCs的靶向癌症能力。荧光显微镜和流式细胞仪数据显示,与对照组相比,FR + ve细胞上高浓度的FA偶联NCs具有高度特异性的结合和细胞摄取。因此,本研究揭示了多种杂质掺杂的稀土氧化物纳米晶体具有独特的双峰对比成像能力,无毒和靶向癌症的能力,可以在分子成像中找到有希望的应用。

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