Unravelling the Properties of Fluorescent Ammonium Salts to Obtain Thixotropic Hydrogels with Antitumoral Activity

Abstract

Novel fluorescent and thixotropic hydrogels, based on naphthalimide salts differing for both the cation and anion structure, were obtained and applied as promising bioimaging and antitumoral agents. First, the photophysical behavior of the salts was analyzed through UV–vis and fluorescence investigation at variable solvent and concentration, together with the determination of the relative fluorescence quantum yield in water. Organic salts were also tested as gelators, and the resulting soft materials, obtained in H2O, H2O/DMSO mixtures, and glycerol, were characterized by rheological measurements and fluorescence and resonance light scattering analyses. Morphology of gel phases was examined via scanning electron microscopy. To assess their therapeutic potential, the salts were tested for cytotoxicity and selectivity against a panel of cancer and normal cell lines using the MTT assay. Their performance as bioimaging agents was also evaluated. Remarkably, all salts exhibited strong fluorescence, and their cytotoxicity effects were closely linked to their chemical structure. Notably, the replacement of bromide with gluconate as an anion significantly enhanced cellular uptake, cytotoxicity, and selectivity toward cancer cells. Release experiments revealed that the mechanism of action of the hydrogel can be ascribed to the release of gelator into aqueous media, enabling the ammonium salts to exert a cytotoxic effect. Collectively, our findings support a mechanism of action in which gluconate-based salts are internalized more efficiently by cancer cells, thereby triggering oxidative stress, mitochondrial dysfunction, and apoptotic cell death. These results highlight gluconate-based salts as dual-function materials with promising applications in both cancer therapy and bioimaging.