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A Cascade-Responsive AND-Logic-Activatable Nanoprobe for Intraoperative Fluorescence Imaging of Colorectal Cancer
Leyi Fang1, Yusuke Ishigaki2, Weijing Huang1
1State Key Laboratory of Analytical Chemistry for Life Science, Department of General Surgery & Pathology, Nanjing Drum Tower Hospital, School of Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University; Nanjing 210023, China.
A new near-infrared fluorescence nanoprobe, duNP-DA, precisely images colorectal cancer during surgery. It activates using tumor-specific conditions, improving tumor detection and margin assessment for better surgical outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Surgical Oncology
Background:
- Current fluorescence (FL) probes for cancer surgery are "always-on" and non-specific, leading to poor tumor visualization.
- Suboptimal tumor-to-background ratios (TBR) hinder accurate assessment of tumor margins during surgery.
Purpose of the Study:
- To develop and evaluate duNP-DA, a novel AND-logic activatable near-infrared (NIR) FL nanoprobe for precise colorectal cancer (CRC) intraoperative imaging.
- To assess duNP-DA's ability to improve tumor detection, margin assessment, and surgical guidance in CRC.
Main Methods:
- Designed duNP-DA, a cascade-responsive nanoprobe utilizing acidic tumor microenvironment (TME) for charge inversion and AND-logic activation by hydrogen sulfide (H2S) and lysosomal pH.
- Evaluated probe kinetics, tumor uptake, and NIR FL enhancement in vitro and in vivo.
- Assessed diagnostic performance, including TBR, lesion detection, and correlation with tumor cellularity in preclinical models and clinical evaluations.
Main Results:
- duNP-DA demonstrated rapid and specific activation within CRC cells via a dual-trigger mechanism (lysosomal pH and H2S).
- Achieved significant NIR FL enhancement (>100-fold) and high TBR (up to 8.2) in primary and metastatic colorectal tumors.
- Successfully delineated small lesions (2 mm), including deep-seated peritoneal metastases, occult lymph nodes, and omental lesions, with 100% diagnostic sensitivity and specificity.
Conclusions:
- duNP-DA offers a promising platform for precise intraoperative imaging and margin assessment in colorectal cancer surgery.
- The nanoprobe's AND-logic activation and high tumor-to-background ratio significantly enhance visualization of tumors and metastatic lesions.
- Clinical evaluations confirm duNP-DA's potential to guide surgical resection and improve patient outcomes in CRC.
