A naphthalimide based fluorescent liposomal system for sequential copper(II) and hydrogen sulfide detection and its...

Hydrogen sulfide (H₂S) is a key endogenous gaseous messenger, and its abnormal levels are closely linked to major physiological and pathological conditions. Developing selective and water-compatible H₂S probes is therefore crucial. In this work, we report an amphiphilic naphthalimide-DPA-based fluorescent probe (Nap.Amp) capable of sequential Cu²⁺ and H₂S detection via a fluorescence ON-OFF-ON mechanism. Nap.Amp exhibits strong green fluorescence that is quenched upon the formation of an in situ copper complex (Nap.Amp-Cu), which in turn displays excellent selectivity toward H₂S, restoring the emission signal through copper displacement. To enhance aqueous solubility and sensing efficiency, Nap.Amp was incorporated into DOPC liposomes to generate nanoscale vesicles (Nap.Lipo). This liposomal system showed significantly improved Cu²⁺ affinity, forming nanoaggregates that served as a sensitive platform for H₂S recognition. The Nap.Lipo-Cu ensemble detected H₂S with a low LOD of 1.62 μM, and the sensing mechanism was validated using DLS and SEM analyses. Beyond solution-phase studies, Nap.Amp-Cu was adapted into portable test formats such as double-chamber gas sensors, paper strips, and alginate hydrogel beads for rapid, instrument-free H₂S detection. Nap.Lipo also demonstrated excellent biocompatibility and enabled fluorescence imaging of H₂S in L929 cells. Overall, this work presents the first demonstration of a liposome-incorporated naphthalimide-DPA probe (Nap.Amp) as a robust, versatile nanosensor for environmental and biological H₂S detection.