Simultaneous Fe <sup>2+</sup> /Fe <sup>3+</sup> imaging shows Fe <sup>3+</sup> over Fe <sup>2+</sup> enrichment in Alzheimer’s disease mouse brain
Yuting Wu, Seyed‐Fakhreddin Torabi, Ryan J. Lake, Shanni Hong, Zhengxin Yu, Peiwen Wu, Zhenglin Yang, Kevin E. Nelson, Weijie Guo, Gregory T. Pawel, Jacqueline Van Stappen, Xiangli Shao, Liviu M. Mirica, Yi Lu
Abstract
Visualizing redox-active metal ions, such as Fe 2+ and Fe 3+ ions, are essential for understanding their roles in biological processes and human diseases. Despite the development of imaging probes and techniques, imaging both Fe 2+ and Fe 3+ 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 Fe 2+ or Fe 3+ , revealing a decreased Fe 3+ /Fe 2+ ratio during ferroptosis and an increased Fe 3+ /Fe 2+ ratio in Alzheimer’s disease mouse brain. The elevated Fe 3+ /Fe 2+ ratio was mainly observed in amyloid plaque regions, suggesting a correlation between amyloid plaques and the accumulation of Fe 3+ and/or conversion of Fe 2+ to Fe 3+ . Our sensors can provide deep insights into the biological roles of labile iron redox cycling.