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@Ag2S‐AF7P) is presented for rapid unperturbed‐tissue analysis for ex vivo and in vivo neuroblastoma diagnosis. A&MMP@Ag2S‐AF7P displays negligible fluorescence in normal tissues but is activated quickly by inhibiting the fluorescence resonance energy transfer (FRET) between Ag2S 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.

Activatable NIR‐II Fluorescent Probes Applied in Biomedicine: Progress and Perspectives

“…Therefore, detecting the concentration of these molecules in vivo has important research significance for prevention and detection of related diseases. In this part, we emphatically describe the representative development of reactive oxygen species (ROS), [70–73] gas, [74,75] enzymes [76–78] and pH sensing [79–81] based on NIR‐II AFPs. In order to broaden the application of NIR‐II AFPs, designs and applications of them are detailed introduction in the following, and representative of NIR‐II AFPs were summarized in Table 2.…”

“…Contained AF7P peptide could target MMP14 and cleave linkers that assembled by multiple components (Figure 4). [76] The obtained NIR‐II nanoprobes have realized the effective diagnosis of neuroblastoma and also provided more possibilities for clinical transformation.…”

Near-Infrared Inorganic Nanomaterials for Precise Diagnosis and Therapy

“…Precise intraoperative histopathological analysis are complicated, which greatly delay the intraoperative decision. Zhan et al (2021) successfully developed matrix metalloproteinase 14 (MMP14) activated (A&MMP@Ag 2 S-AF7P) for accurate NIR imaging diagnosis of neuroblastoma (NB). In this nanoprobe, the affinity peptide can help to recognize and target the NB cells by overexpressed matrix metalloproteinase 14.…”

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

“…In particular, inhibiting cancer cell-derived MMPs could increase the stability of the endogenous ECM barrier and thus prevent cancer cells from breaking the basement membrane, which in turn would reduce or even suppress metastases [439,440]. In order to precisely identify tumor tissue during tumor surgery, an MMP-cleavable FRET probe that is internalized by cancer cells has been developed [441]. Elevated serum levels of soluble MMP-14 are a marker for poor prognosis and possibly indicate the presence of distant metastases [442].…”