Universidade da Coruña, Departamento de Química y Centro de Investigacións Científicas Avanzadas, E-15071 A, Coruña, Spain.
Medical University of Vienna, Department of Medicine I, Institute of Cancer Research and Comprehensive Cancer Center, Borschkegasse 8a, A-1090, Vienna, Austria.
Angew Chem Int Ed Engl. 2019 Jun 11;58(24):8007-8012. doi: 10.1002/anie.201900934. Epub 2019 May 8.
Metal-driven self-assembly afforded a multitude of fascinating supramolecular coordination complexes (SCCs) with applications as catalysts, host-guest, and stimuli-responsive systems. However, the interest in the biological applications of SCCs is only starting to emerge and thorough characterization of their behavior in biological milieus is still lacking. Herein, we report on the synthesis and detailed in-cell tracking of a Pt L metallacycle. We show that our hexagonal supramolecule accumulates in cancer cell nuclei, exerting a distinctive blue fluorescence staining of chromatin resistant to UV photobleaching selectively in nucleolar G4-rich regions. SCC co-localizes with epitopes of the quadruplex-specific antibody BG4 and replaces other well-known G4 stabilizers. Moreover, the photophysical changes accompanying the metallacycle binding to G4s in solution (fluorescence quenching, absorption enhancement) also take place intracellularly, allowing its subcellular interaction tracking.
金属驱动的自组装提供了多种迷人的超分子配位化合物(SCCs),它们可作为催化剂、主体-客体和刺激响应系统。然而,SCC 在生物应用方面的兴趣才刚刚开始显现,其在生物环境中的行为仍缺乏深入的表征。在此,我们报告了一种 Pt L 金属环的合成和详细的细胞内追踪。我们表明,我们的六方超分子在癌细胞核中积累,选择性地在富含 G4 的核仁区域中对染色质施加独特的蓝色荧光染色,该染色质对 UV 光漂白具有抗性。SCC 与四链体特异性抗体 BG4 的表位共定位,并取代其他众所周知的 G4 稳定剂。此外,金属环与溶液中 G4 结合伴随的光物理变化(荧光猝灭,吸收增强)也在细胞内发生,允许其亚细胞相互作用跟踪。