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.