Lysosome-Targeted Naphthalimide-Based Fluorescence for the Detection of Fe(III) and Monitoring of Iron Metabolism.

Iron is crucial for numerous biological processes, and lysosomes play an essential role in iron metabolism by regulating Fe3+ levels. Disruptions of this regulation can lead to Fe3+ accumulation, resulting in membrane damage and ferroptosis. Here, we have developed a water-soluble fluorescent probe BiNIT that specifically targets lysosomes for the selective detection of Fe3+. BiNIT features a bis-naphthalimide structure linked by a thiophene moiety and incorporates two quaternary ammonium groups, which enhance its ability to target lysosomes and its solubility in aqueous environments. The probe showed high selectivity for Fe3+, with fluorescence quenching resulting from the paramagnetism of Fe3+ and its capacity to induce probe aggregation. This aggregation occurs through coordination bonds between Fe3+ and the carbonyl oxygen, imide nitrogen, or thiophene sulfur in multiple probe molecules. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) confirmed the formation of nanoparticles upon Fe3+ binding. Moreover, BiNIT remains stable in environments with pH values above 4, facilitating precise monitoring of Fe3+ levels within lysosomes. This innovative tool provides valuable insights into iron homeostasis, oxidative stress, and ferroptosis, aiding research on iron-related diseases and the development of therapeutic strategies.