Rapid Unperturbed‐Tissue Analysis for Intraoperative Cancer Diagnosis Using an Enzyme‐Activated NIR‐II Nanoprobe

Abstract Accurate intraoperative tissue identification is critical to tumor surgery. However, conventional methods are labor‐ and time‐intensive, which greatly delay the intraoperative decision‐making. Herein, a matrix metalloproteinase (MMP)14‐activated NIR‐II nanoprobe (A&MMP@Ag 2 S‐AF7P) is presented for rapid unperturbed‐tissue analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag 2 S‐AF7P displays negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) between Ag 2 S QDs and A1094 mediated by MMP14 overexpressed in neuroblastoma; meanwhile, the exposure of the membrane penetrating peptide R9 (TAT‐peptide) results in efficient internalization of nanoprobes in the cancer cells, providing superior tumor‐to‐normal (T/N) tissue ratio. Instant illumination of the lesion and well‐defined tumor margins make the nanoprobes a suitable rapid diagnostic reagent for cancer surgical or tissue biopsy procedures.