A Hf(IV)‐Coordinated NIR‐II Fluorescence “Turn‐On” Nanoprobe for Precise Imaging‐Guided Surgery in Breast Cancer

Abstract Breast‐conserving surgery (BCS) has become the standard care for early‐stage breast cancer. The accurate assessment of tumor margins is urgently required for BCS because positive resection margins often lead to local recurrence. To address this clinical dilemma, a Hf(IV)‐coordinated NIR‐II fluorescence “turn‐on” nanoprobe based on the clinically approved NIR‐II fluorescent dye indocyanine green (ICG) for intraoperative tumor visualization is developed. Notably, the fluorescence of ICG can be efficiently quenched by Hf(IV) and subsequently recovered in vivo, showing a remarkable fluorescence “quenching‐recovery‐amplification” capacity. This nanoprobe can effectively accumulate in tumor sites, accurately identifying submillimeter‐sized primary and residual tumors with high sensitivity. In addition, subcutaneous, muscle‐infiltrating, and orthotopic breast cancer models are built to repeatedly prove that this ultrasensitive nanoprobe is feasible for precise imaging‐guided surgery in breast cancer. Overall, this study constructs an activatable fluorescent nanoprobe for real‐time intraoperative tumor margin visualization, holding promise for complete surgical resection and reduction of local recurrence.