Engineering Acid-Promoted Two-Photon Ratiometric Nanoprobes for Evaluating HClO in Lysosomes and Inflammatory Bowel Disease.

HClO is considered a potential contributing factor and biomarker of inflammatory bowel disease (IBD). Accurate monitoring of lysosomal HClO is important for further developing specific diagnostic and therapeutic schedules for IBD. However, only rare types of fluorescent probes have been reported for detecting HClO in IBD so far. Herein, an acid-promoted two-photon semiconducting polymer dot (Lyso-RS Pdot) with dual emission in green and red channels and dual-sensing sites is successfully fabricated with two newly designed polymers NADE-PSMA and PFNA-10TBT as precursors. The red conjugated polymer PFNA-10TBT with pH-inert and HClO-sensitive units is employed to evaluate the HClO concentration in turn-off fluorescence. Meanwhile, the amphiphilic green fluorescent polymer NADE-PSMA sensitive to pH and HClO is employed to evaluate the pH value or HClO concentration in turn-on fluorescence. The resultant Lyso-RS Pdots not only display satisfactory performances for detecting HClO and pH but also achieve accurate two-photon imaging of HClO in lysosomes and the colon of IBD mice based on the distinguished properties such as ratiometric signal output, acid-promoted signal amplification, ultrafast response, and two-photon excitation. The results demonstrate that the HClO level in IBD mice is elevated, and the fast early diagnosis of IBD can be achieved through fluorescence imaging by the proposed Lyso-RS Pdots. This work may provide some solid perspectives for fluorescent diagnosis of H and HClO-related diseases.