College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , China.
J Am Chem Soc. 2019 Dec 4;141(48):18964-18969. doi: 10.1021/jacs.9b11024. Epub 2019 Nov 22.
As a monolayered version of nanoscale metal-organic frameworks (nMOFs), nanoscale metal-organic layers (nMOLs) represent an emerging class of highly tunable two-dimensional materials for hierarchical functionalization and with facile access to analytes. Here we report the design of the first nMOL-based biosensor for ratiometric pH and oxygen sensing in mitochondria. Cationic Hf-Ru nMOL was solvothermally synthesized by laterally connecting Hf secondary building units (SBUs) with oxygen-sensitive Ru(bpy)-derived DBB-Ru ligands (bpy = 2,2'-bipyridine). The Hf-Ru nMOL was then covalently functionalized with pH-sensitive fluorescein isothiocyanate and pH/oxygen-independent Rhodamine-B isothiocyanate through thiourea linkages to afford Hf-Ru-F/R as a mitochondria-targeted ratiometric sensor for pH and O in live cells. High-resolution confocal microscope imaging with Hf-Ru-F/R revealed a positive correlation between pH and local O concentration in mitochondria. Our work shows the potential of nMOL-based ratiometric biosensors in sensing and imaging of biologically important analytes in live cells.
作为纳米级金属有机骨架（nMOFs）的单层版本，纳米级金属有机层（nMOLs）代表了一类新兴的高度可调谐二维材料，可用于分层功能化，并易于接近分析物。在这里，我们报告了第一个基于 nMOL 的生物传感器的设计，用于线粒体中的比率 pH 和氧传感。通过横向连接 Hf 次级建筑单元（SBUs）和氧敏感的 Ru（bpy）衍生的 DBB-Ru 配体（bpy = 2,2'-联吡啶），溶剂热合成了阳离子 Hf-Ru nMOL。然后，通过硫脲键将 pH 敏感的荧光素异硫氰酸酯和 pH/氧独立的罗丹明 B 异硫氰酸酯共价功能化，得到 Hf-Ru-F/R，作为用于活细胞中 pH 和 O 的线粒体靶向比率传感器。使用 Hf-Ru-F/R 的高分辨率共聚焦显微镜成像显示，线粒体中 pH 和局部 O 浓度之间存在正相关关系。我们的工作表明，基于 nMOL 的比率生物传感器在活细胞中对生物重要分析物的传感和成像具有潜力。
