A H2S-activated NIR-II imaging probe for precise diagnosis and pathological evaluation of colorectal tumor

Rationale: The quick and accurate detection of colorectal cancer (CRC) is essential for improving the treatment efficacy and patient survival, which nevertheless remains challenging due to low specificity and sensitivity of current CRC diagnostic approaches. Therefore, providing a robust solution for real-time and accurate tumor delineation is highly desirable. Methods: We report a novel polyacrylic acid-mediated strategy to develop the endogenous hydrogen sulfide (H₂S)-activated NIR-II probe DCNP@PB for specific visualization of CRC and image-guided tumor surgery. The stability, biocompatibility, H₂S-responsiveness, and NIR-II imaging capability were evaluated in vitro and in vivo. Human CRC tissues were used to evaluated the performance of the DCNP@PB. Results: By exploiting the effective inner filter effect (IFE) and fluorescence resonance energy transfer (FRET) between DCNPs and PB, luminescence of DCNP@PB can be rapidly switched ON in response to H₂S in colorectal tumor, affording high tumor-to-background ratio (TBR). Notably, H₂S-responsive range of DCNP@PB well matches the H₂S concentration at tumor site, thereby minimizing nonspecific activation by other sulfur-containing substances in a complicated biological environment. Such accurate H₂S responsiveness not only benefits the differentiation between tumor and normal tissues in the mouse model, but also clearly delineates the cancerous boundaries in human tissues specimens. Conclusion: This work presents not only a promising example of H₂S-activated NIR-II optical probe that could be intravenously injected for in vivo applications to afford reliable information and quick feedback, but also an effective strategy to design the activatable imaging probes for precise tumor diagnosis and intraoperative decision support.