Simultaneous Fe²⁺/Fe³⁺ imaging shows Fe³⁺ over Fe²⁺ enrichment in Alzheimer's disease mouse brain

Visualizing redox-active metal ions, such as Fe²⁺ and Fe³⁺ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe²⁺ and Fe³⁺ simultaneously in living cells with high selectivity and sensitivity has not been reported. Here, we selected and developed DNAzyme-based fluorescent turn-on sensors that are selective for either Fe²⁺ or Fe³⁺, revealing a decreased Fe³⁺/Fe²⁺ ratio during ferroptosis and an increased Fe³⁺/Fe²⁺ ratio in Alzheimer's disease mouse brain. The elevated Fe³⁺/Fe²⁺ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe³⁺ and/or conversion of Fe²⁺ to Fe³⁺. Our sensors can provide deep insights into the biological roles of labile iron redox cycling.