Nanoscale\nMetal–Organic Layers Detect Mitochondrial\nDysregulation and Chemoresistance via Ratiometric Sensing of Glutathione\nand pH

Abstract

Mitochondrial dysregulation controls\ncell death and survival by\nchanging endogenous molecule concentrations and ion flows across the\nmembrane. Here, we report the design of a triply emissive nanoscale\nmetal–organic layer (nMOL), NA@Zr-BTB/F/R, for sensing mitochondrial\ndysregulation. Zr-BTB nMOL containing Zr₆ secondary building\nunits (SBUs) and 2,4,6-tris­(4-carboxyphenyl)­aniline (BTB-NH₂) ligands was postsynthetically functionalized to afford NA@Zr-BTB/F/R\nby exchanging formate capping groups on the SBUs with glutathione­(GSH)-selective\n(2<i>E</i>)-1-(2′-naphthyl)-3-(4-carboxyphenyl)-2-propen-1-one\n(NA) and covalent conjugation of pH-sensitive fluorescein (F) and\nGSH/pH-independent rhodamine-B (R) to the BTB-NH₂ ligands.\nCell imaging demonstrated NA@Zr-BTB/F/R as a ratiometric sensor for\nmitochondrial dysregulation and chemotherapy resistance via GSH and\npH sensing.