A Mitochondria-Targeted Fluorescence/Photoacoustic Dual-Modality imaging probe for Hypochlorous Acid-Related inflammatory Responses in vivo

• MB-TPP achieves excellent NIRF/PA dual-modality imaging in RA mouse model. • MB-TPP shows excellent selectivity, high sensitivity, and rapidly detect HClO (< 5 s). • MB-TPP targets mitochondria with Pearson’s coefficient of 0.83. • MB-TPP performs linear quantitative NIRF/PA imaging of HClO in vitro. Hypochlorous acid (HClO) is a crucial endogenous reactive oxygen species (ROS) that is widely regarded as a representative of ROS. The excessive accumulation of HClO has been intimately linked to tissue damage and a myriad of diseases. Notably, mitochondria, the primary energy factories within cells, also serve as crucial sites for the generation of HClO. Consequently, the detection of intracellular mitochondrial HClO holds significant importance. In this study, we have designed and synthesized a novel near-infrared fluorescence (NIRF)/photoacoustic (PA) dual-modality probe, designated as MB-TPP. MB-TPP exhibits outstanding selectivity towards HClO, rapid fluorescence switching response (< 5 s). MB-TPP demonstrates remarkable sensitivity for HClO detection ( LOD = 0.075 μM). Furthermore, MB-TPP possesses favorable water solubility and mitochondrial targeting capability. The application of MB-TPP has been validated in biological models such as zebrafish and mice, where it achieves excellent NIRF imaging of endogenous and exogenous HClO. Remarkably, MB-TPP possesses the capability to perform PA imaging of HClO ex vivo , exhibiting a linear detection efficiency. Moreover, MB-TPP demonstrated its capability for NIRF/PA dual-modality imaging in the mice model of rheumatoid arthritis. As a powerful NIRF/PA imaging visualization tool, MB-TPP holds immense promise for monitoring and investigating HClO-related inflammatory diseases, particularly those associated with mitochondrial function in biological contexts, thereby underscoring its broad application potential and significant value in the fields of biomedical research and clinical diagnostics.