A pair of inverse ratiometric sensing paradigms based on stimulus response of AIE@ZIFs via solvent-assisted aggregation-induced emission modulation and substituent-dependent ligand emission regulation for dynamic monitoring of PFAS-induced ATP changes in cardiomyocytes.

Two aggregation-induced emission (AIE) guests, tetra[4-(3,5-dicarboxyphenyl)] tetraphenylethylene (H8ETTB) and dispersed Cu nanoclusters (D-CuNCs), were separately encapsulated into ZIF-8 and ZIF-90, which bear methyl-substituted and aldehyde-functionalized imidazole ligands, respectively. The constructed AIE@ZIFs (H8ETTB@ZIF-8 and A-CuNCs@ZIF-90) integrate dual emissions from the guests and the intrinsic ligand emission (LE) of the ZIF skeletons. Based on ATP-triggered responses, we developed inverse ratiometric sensing paradigms through solvent-assisted AIE modulation and substituent-dependent LE regulation, which have been rarely explored. The distinct fluorescence color changes (bluish-green to green; orange-red to blue), arising from opposite emission responses of the guests and ligands, enable reliable color-oriented analysis. H8ETTB@ZIF-8 affords a linear range of 0.02-6 mM ATP with detection limits of 9.84 µM (spectral) and 19.86 µM (smartphone), while A-CuNCs@ZIF-90 exhibits a linear range of 0.01-3 mM with limits of 4.26 µM and 8.52 µM, respectively. Both nanoprobes show outstanding anti-interference performance and can be internalized into cardiomyocytes (H9c2) for in situ imaging of ATP dynamics and accurate quantification of PFAS-induced ATP perturbations. Mitochondrial ATP loss is validated as an appropriate cardiotoxicity indicator for PFOS and PFOA, thereby advancing the toxicological assessment of emerging pollutants.