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Rapid and Nondestructive Histopathological Analysis for Intraoperative Cancer Diagnosis Using an Enzyme-Activated NIR-II Nanoprobe.

Accurate intraoperative histopathological analysis is critical to the 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 and nondestructive histopathological analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag 2 S-AF7P displays the negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) process 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 adequate as rapid diagnostic reagent for incorporation into cancer surgical or tissue biopsy procedures.