Single Side‐Chain‐Modulatory of Hemicyanine for Optimized Fluorescence and Photoacoustic Dual‐Modality Imaging of H2S In Vivo

Abstract Near‐infrared fluorescence (NIRF)/photoacoustic (PA) dual‐modality imaging integrated high‐sensitivity fluorescence imaging with deep‐penetration PA imaging has been recognized as a reliable tool for disease detection and diagnosis. However, it remains an immense challenge for a molecule probe to achieve the optimal NIRF and PA imaging by adjusting the energy allocation between radiative transition and nonradiative transition. Herein, a simple but effective strategy is reported to engineer a NIRF/PA dual‐modality probe (Cl‐HDN3) based on the near‐infrared hemicyanine scaffold to optimize the energy allocation between radiative and nonradiative transition. Upon activation by H2S, the Cl‐HDN3 shows a 3.6‐fold enhancement in the PA signal and a 4.3‐fold enhancement in the fluorescence signal. To achieve the sensitive and selective detection of H2S in vivo, the Cl‐HDN3 is encapsulated within an amphiphilic lipid (DSPE‐PEG2000) to form the Cl‐HDN3‐LP, which can successfully map the changes of H2S in a tumor‐bearing mouse model with the NIRF/PA dual‐modality imaging. This work presents a promising strategy for optimizing fluorescence and PA effects in a molecule probe, which may be extended to the NIRF/PA dual‐modality imaging of other disease‐relevant biomarkers.