Highly Selective Dual-Modal Probe for Photoacoustic and Magnetic Resonance Imaging of the Labile Cu 2+ Pool in the Liver

作者：Zhao‐Qing Liu, Lei Zhang, Sha Li, Long Xiao, Yu Qiao, Yue Zhu, Yingying Luo, Maosong Qiu, Xin Zhou, Shizhen Chen · 发表于：Analytical Chemistry · 年份：2025 · DOI：10.1021/acs.analchem.5c03093 · 被引用次数：4 · 研究领域：Spectroscopy Techniques in Biomedical and Chemical Research、Protein Interaction Studies and Fluorescence Analysis、Photoacoustic and Ultrasonic Imaging

Copper ions (Cu 2+ ) play vital roles in human physiology, and their dyshomeostasis is associated with diseases such as hepatocellular carcinoma, Alzheimer’s disease, and Wilson’s disease. Cu 2+ imaging technologies facilitate the investigation of Cu 2+ dynamics in biological systems. However, developing highly selective and sensitive Cu 2+ probes that can overcome interference from physiologically abundant Zn 2+ remains a key challenge. In this study, we design and synthesize a Cu 2+ -activated dual-modal probe ( BHGd ) for photoacoustic (PA) and magnetic resonance (MR) imaging, which exhibits remarkable specificity for Cu 2+ . Impressively, BHGd demonstrates exceptional selectivity for Cu 2+ even in the presence of a 1000-fold excess of Zn 2+ . BHGd binds Cu 2+ in a 1:1 stoichiometry, forming a stable ternary complex in the presence of human serum albumin (HSA), which enhances PA signals by 5.9-fold and increases longitudinal relaxivity ( r 1 ) by 114.9%. Furthermore, in vivo experiments demonstrate that BHGd enables precise monitoring of labile Cu 2+ fluctuations in the liver of mice, achieving a remarkable 59% increase in PA signal intensity and a 30% enhancement in MR signal contrast. The systematic investigation demonstrates that BHGd can serve as a powerful molecular probe for investigating copper metabolism in living systems. Our breakthrough addresses the long-standing challenge of Cu 2+ /Zn 2+ discrimination and provides a design principle for next-generation metal ...