Fluorine-Functionalized Isophorone Near-Infrared Cu2+ Fluorescent Probe for Lung-Targeted Imaging of Diabetic Lung Injury and Lung Cancer
Jinping Shao, Xiaotong An, Cong Zhang, Yani Huang, Lijun Fang, YuShuang Pu, Shuang Li, Jianmei Chen, Li Xu, Zhenpeng Qiu, Shumin FengAbstract
Traditional small-molecule fluorescent probes suffer from nonspecific accumulation in metabolic organs, limiting their application in lung disease monitoring. Herein, we developed a fluorine-substituted dicyanoisophorone-based probe (PFCu) with picolinate as the Cu2+-recognition moiety. PFCu preferentially illuminated A549 cancer cells and exhibited remarkable lung-targeting accumulation, enabling specific Cu2+ recognition in the lung. The probe allows real-time monitoring of Cu2+ level in living cells and possesses ER-targeting ability, facilitating analysis of Cu2+ fluctuations in high glucose-induced diabetic models and revealing the relationship among hyperglycemia, ER stress, and copper homeostasis. Notably, PFCu effectively distinguished lung tumor-bearing mice from healthy controls and showed significantly higher fluorescence in tumor tissues than in adjacent normal tissues from clinical samples. This study provides a novel molecular tool for lung disease research, supports Cu2+ as a potential biomarker for early diagnosis of lung cancer, and offers new strategies for diagnosing Cu2+-related diseases.