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首页> 外文期刊>Chemistry: A European journal >Cell-specific and nuclear targeting with [M(CO)(3)](+) (M=Tc-99m, Re)-based complexes conjugated to acridine orange and bombesin
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Cell-specific and nuclear targeting with [M(CO)(3)](+) (M=Tc-99m, Re)-based complexes conjugated to acridine orange and bombesin

机译：与[M（CO）（3）]（+）（M = Tc-99m，Re）的复合物与a啶橙和蛙皮素共轭，进行细胞特异性和核靶向

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Receptor-specific nuclear targeting requires trifunctional metal complexes. We have synthesized [M(L (2)-pept)(L-1-acr)(CO)(3)] (pept = peptide; acr=acridine-based agent) in which the fac-[M(CO)(3)](+) moiety (1st function, M=Tc-99m, Re) couples an acridine-based nuclear-targeting agent (2nd function, L-1-acr) and the specific cell-receptor-binding peptide bombesin (3rd function, L-2-pept). The metal-mediated coupling is based on the mixed ligand [2+1] principle. The nuclear targeting agents have been derivatised with an isocyanide group for monodentate (L-1) and bombesin (BBN) with a bidentate ligand (L-2) for complexation to fac-[M(CO)(3)](+). For nuclear uptake studies, the model complexes [Re(L-2) (C-acr)(CO)(3)] (L-2 = pyridine-2-carboxylic acid and pyridine-2,4-dicarboxylic acid) were synthesized and structurally characterized. We selected acridine derivatives as nuclear-targeting agents, because they are very good nucleus-staining agents and exhibit strong fluorescence. Despite the bulky metal complexes attached to acridine, all [Re(L-2) (L-1-acr)(CO)(3)] showed high accumulation in the nuclei of PC3 and B16F1 cells, as evidenced by fluorescence microscopy. For radiopharmaceutical purposes, the Tc-99m analogues have been prepared and radioactivity distribution confirmed the fluorescence results. Coupling of BBN to L-2 gave the receptor-selective complexes [M(L-2-BBN)(L-1-acr)(CO)(3)]. Whereas no internalization was found with B16F1 cells, fluorescence microscopy on PC3 cells bearing the BBN receptor showed high and rapid uptake by receptor-mediated endocytosis into the cytoplasm, but not into the nucleus.
机译：受体特异性核靶向需要三官能金属配合物。我们合成了[M（L（2）-pept）（L-1-acr）（CO）（3）]（pept =肽; acr =基于r啶的试剂），其中fac- [M（CO）（ 3）]（+）部分（第一个功能，M = Tc-99m，Re）将a啶基核靶向剂（第二个功能，L-1-acr）与特定的细胞受体结合肽蛙皮素（第三个功能）偶联功能，L-2-pept）。金属介导的偶联基于混合配体[2 + 1]原理。核靶向剂已被单齿（L-1）的异氰基衍生化，而具有双齿配体（L-2）的蛙皮蛋白（BBN）衍生化成fac- [M（CO）（3）]（+）。为了进行核吸收研究，合成了模型配合物[Re（L-2）（C-acr）（CO）（3）]（L-2 =吡啶-2-羧酸和吡啶-2,4-二羧酸）和结构上的特点。我们选择a啶衍生物作为核靶向剂，因为它们是非常好的核染色剂，并且显示出强荧光。尽管笨重的金属络合物附着在a啶上，但所有[Re（L-2）（L-1-acr）（CO）（3）]在PC3和B16F1细胞核中均显示出高积累，如荧光显微镜所证明的。为了放射性药物的目的，已经制备了Tc-99m类似物，并且放射性分布证实了荧光结果。 BBN与L-2的偶联产生受体选择性复合物[M（L-2-BBN）（L-1-acr）（CO）（3）]。 B16F1细胞未发现内在化作用，而携带BBN受体的PC3细胞的荧光显微镜检查显示，受体介导的内吞作用可快速且快速地摄取到细胞质中，而不吸收到细胞核中。

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