State Lab of Analytical Chemistry for Life Science (MOE), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, People's Republic of China.
Anal Chem. 2012 May 1;84(9):4140-6. doi: 10.1021/ac3003402. Epub 2012 Apr 17.
As an emerging category of fluorescent metal nanoclusters, oligonucleotide-templated silver nanoclusters (Ag NCs) have attracted a lot of interest and have shown wide application in biorelated disciplines. However, the weak fluorescence emission and poor permeability to cell membranes tethered further intracellular applications of Ag NCs. AS1411 is an antiproliferative G-rich phosphodiester oligonucleotide and currently an anticancer agent under phase II clinical trials. Herein, we present a strategy to synthesize AS1411-functionalized Ag NCs with excellent fluorescence through a facile one-pot process. Confocal laser scanning microscopy and Z-axis scanning confirmed that the AS1411-functionalized Ag NCs could be internalized into MCF-7 human breast cancer cells and were able to specifically stain nuclei with red color. To our surprise, 3-[4,5-dimethylthiazol-z-yl]-2,5-diphenyltetrazolium bromide (MTT) assay demonstrated the Ag NCs were cytocompatible and showed better inhibition effects than pure AS1411 on MCF-7 human breast cancer cells. In addition, a universal design of the oligonucleotide scaffold for synthesis of Ag NCs was extended to other aptamers, such as Sgc8c and mucin 1 aptamer. Due to the facile synthesis procedure and capability of specific target recognition, this fluorescent platform will potentially broaden the applications of Ag NCs in biosensing and biological imaging.
作为一类新兴的荧光金属纳米簇，寡核苷酸模板银纳米簇（Ag NCs）引起了广泛关注，并在生物相关学科中显示出广泛的应用。然而，弱荧光发射和较差的细胞膜通透性限制了 Ag NCs 在细胞内的进一步应用。AS1411 是一种具有抗增殖作用的富含 G 的磷酸二酯寡核苷酸，目前正在进行 II 期临床试验的抗癌药物。在此，我们提出了一种通过简便的一锅法合成具有优异荧光的 AS1411 功能化 Ag NCs 的策略。共聚焦激光扫描显微镜和 Z 轴扫描证实，AS1411 功能化的 Ag NCs 可以被内化到 MCF-7 人乳腺癌细胞中，并能够特异性地用红色染色细胞核。令我们惊讶的是，3-[4,5-二甲基噻唑-z-yl]-2,5-二苯基四氮唑溴盐（MTT）测定表明 Ag NCs 具有细胞相容性，并且对 MCF-7 人乳腺癌细胞的抑制作用优于纯 AS1411。此外，寡核苷酸支架的通用设计用于合成 Ag NCs 被扩展到其他适体，如 Sgc8c 和粘蛋白 1 适体。由于其简便的合成程序和特定靶标识别的能力，这种荧光平台将有可能拓宽 Ag NCs 在生物传感和生物成像中的应用。
