An Estrogen Receptor α-Targeted NIR-II Probe for Breast Tumor Imaging and Image-Guided Surgery

Breast cancer (BC) is a serious health threat to women worldwide and is on the steady rise in morbidity and mortality, of which estrogen receptor α (ERα)-positive cases account for nearly 70%. ERα is highly expressed in ERα-positive (ERα+) BC, and it is involved in tumorigenesis and metastasis, making it a compelling target for BC theranostics. Herein, we developed and evaluated an ERα-targeted fluorescent probe (IRDye800-4OHT) by conjugating ERα targeting ligand 4-hydroxytamoxifen with near-infrared fluorescence dye IRDye800CW for ERα+ BC detection via imaging ERα. The probe demonstrated a second near-infrared (NIR-II) imaging capability (λ_em = 950 nm), high binding affinity (RBA = 2.3) toward ERα, and excellent biocompatibility. <i>In vitro</i> cellular uptake further confirmed that IRDye800-4OHT could specifically target the ERα. Moreover, <i>in vivo</i> NIR-II imaging clearly revealed that IRDye800-4OHT enabled real-time imaging of ERα, specifically illuminated tumor tissue, and successfully guided breast tumor resection. Therefore, we postulate that IRDye800-4OHT can serve as a valuable tool for the precise diagnosis and surgical excision of ERα-positive tumors.