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金纳米粒子探针:设计及在体外应用于癌细胞培养

Gold nanoparticle probes: design and in vitro applications in cancer cell culture.

机构信息

Ege University, Faculty of Science, Biochemistry Department, Bornova 35100, Izmir, Turkey.

出版信息

Colloids Surf B Biointerfaces. 2012 Feb 1;90:217-26. doi: 10.1016/j.colsurfb.2011.10.027. Epub 2011 Oct 20.

Abstract

A new architecture has been designed by the conjugation of [(18)F]2-fluoro-2-deoxy-D-glucose ((18)F-FDG), gold nanoparticles (AuNPs), and anti-metadherin (Anti-MTDH) antibody which is specific to the metadherin (MTDH) over-expressed on the surface of breast cancer cells. Mannose triflate molecule is used as a precursor for synthesis of (18)F-FDG by nucleophilic fluorination. For the conjugation of (18)F-FDG and AuNPs, cysteamine was first bound to mannose triflate (Man-CA) before synthesizing of (18)F-FDG which has cysteamine sides ((18)FDG-CA). Then, (18)FDG-CA was reacted with HAuCl(4) to obtain AuNPs and with NaBH(4) for reduction of AuNPs. At the end of this procedure, AuNPs were conjugated to (18)F-FDG via disulphide bonds ((18)FDG-AuNP). For the conjugation of Anti-MTDH, 1,1'-carbonyl diimidazol (CDI) was bound to the (18)FDG-AuNP, and Anti-MTDH was conjugated via CDI ((18)FDG-AuNP-Anti-MTDH). This procedure was also performed by using Na(19)F to obtain non-radioactive conjugates ((19)FDG-AuNP-Anti-MTDH). Scanning electron microscopy (SEM) images demonstrated that synthesized particles were in nano sizes. (18)FDG-AuNP-Anti-MTDH conjugate was characterized and used as a model probe containing both radioactive and optical labels together as well as the biological target. The (18)FDG-AuNP-Anti-MTDH conjugate was applied to MCF7 breast cancer cell line and apoptotic cell ratio was found to be increasing from 2% to 20% following the treatment. Hence, these results have promised an important application potential of this conjugate in cancer research.

摘要

一种新的架构是通过将 [(18)F]2-氟-2-脱氧-D-葡萄糖 ((18)F-FDG)、金纳米粒子 (AuNPs) 和针对乳腺癌细胞表面过度表达的 metadherin (MTDH) 的抗 metadherin (Anti-MTDH) 抗体结合而设计的。三氟甲磺酸甲酯分子被用作亲核氟化合成 (18)F-FDG 的前体。为了将 (18)F-FDG 和 AuNPs 结合,首先将半胱氨酸与三氟甲磺酸甲酯 (Man-CA) 结合,然后再合成具有半胱氨酸侧链的 (18)FDG-CA ((18)FDG-CA)。然后,(18)FDG-CA 与 HAuCl(4) 反应得到 AuNPs,并用 NaBH(4) 还原 AuNPs。在这个过程的最后,AuNPs 通过二硫键与 (18)F-FDG 结合 ((18)FDG-AuNP)。为了将 Anti-MTDH 结合,1,1'-羰基二咪唑 (CDI) 与 (18)FDG-AuNP 结合,然后通过 CDI 将 Anti-MTDH 结合 ((18)FDG-AuNP-Anti-MTDH)。该过程也通过使用 Na(19)F 来获得非放射性缀合物 ((19)FDG-AuNP-Anti-MTDH)。扫描电子显微镜 (SEM) 图像表明合成的颗粒为纳米尺寸。对 (18)FDG-AuNP-Anti-MTDH 缀合物进行了表征,并用作同时含有放射性和光学标记以及生物靶标的模型探针。将 (18)FDG-AuNP-Anti-MTDH 缀合物应用于 MCF7 乳腺癌细胞系,发现随着处理的进行,凋亡细胞比例从 2%增加到 20%。因此,这些结果预示着该缀合物在癌症研究中有重要的应用潜力。

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