Single wavelength excited multi-channel nanoMOFs sensor for simultaneous and ratiometric imaging of intracellular pH and O2

Despite the fact that multi-channel sensors could afford comprehensive information for the analysis of basic biological or physiological processes, the design of such nanosensors based on luminescent metal–organic frameworks (LMOFs) is still in its infancy. Herein, we constructed a three-channel ratiometric LMOF-based nanoprobe using an in situ one-pot strategy in which a pH sensitive organic dye of fluorescein isothiocyanate, an O2 indicator of platinum meso-tetra(4-carboxyphenyl)porphyrin and a reference dye of 1,3,6,8-tetra(4-carboxylphenyl)pyrene were simultaneously integrated into a matrix of UiO-66 nanoparticles. The contents of the encapsulated dyes were precisely mediated to meet the requirement of simultaneous sensing of different signals. The developed LMOF-based nanoprobe demonstrated remarkable sensitivity toward simultaneous pH and O2 detection with good reversibility and could work under single wavelength excitation without signal cross-talk. Given the excellent biocompatibility of UiO-66, the developed multi-channel imaging system was successfully applied to record the response process of cancer cells to external acidity and oxygenation changes, especially in hypoxia and low acidity. Thanks to the integration of different luminescent reporters in the MOF substrate, the nanoprobe could work as a whole to concomitantly image and quantify different signals at the same location in living cancer cells, prefiguring the great promise of the current strategy for the design of a large variety of sensing platforms towards the analysis of multiple biological signals.