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

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@Ag₂ S-AF7P) is presented for rapid unperturbed-tissue analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag₂ S-AF7P displays negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) between Ag₂ 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.