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

Abstract

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.