Bioimaging of labile lysosomal iron through naphthalimide-based fluorescent probe

Lysosomal labile iron detection is immensely important as it is related to various diseases like Alzheimer's disease, Huntington's disease, Parkinson's disease, and cell apoptosis like ferroptosis. The fluorescent-based detection methods are preferred due to their sensitive, non-invasive, and spatial-temporal detection in biological samples. However, this remains a great challenge due to the lysosomal compartment being acidic alters the photophysical properties of the probe. Herein, we have rationally designed and synthesized multi-component naphthalimide-based fluorescent marker with preferred optical properties and bio-compatibility for selective detection of labile iron present in the lysosomal compartment. The synthesized probe was characterized structurally and optically by NMR, mass spectrometry, UV-visible, and fluorescence spectroscopy. The developed probe with an appropriate linking strategy turns out to be tolerant to fluorescence alternation in lysosomal pH. The probe exhibits great selectivity and high sensitivity for Fe(III) with limit of detection of 0.44 μM and is also able to detect Fenton-type reactions. Further, the probe has been successfully applied for lysosomal imaging and detecting labile Fe(III) present in the lysosomal lumen of the live cells.