Single Side-Chain-Modulatory of Hemicyanine for Optimized Fluorescence and Photoacoustic Dual-Modality Imaging of HS In Vivo.

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-HDN) based on the near-infrared hemicyanine scaffold to optimize the energy allocation between radiative and nonradiative transition. Upon activation by HS, the Cl-HDN 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 HS in vivo, the Cl-HDN is encapsulated within an amphiphilic lipid (DSPE-PEG) to form the Cl-HDN-LP, which can successfully map the changes of HS 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.