Abstract Heart failure (HF), a major global health challenge with high morbidity and mortality, lacks effective biomarkers and non‐invasive tools for early diagnosis and therapy evaluation. Endogenous carbon monoxide (CO), a key biological signaling molecule, is closely linked to cardiovascular diseases such as HF when dysregulated. Integrating near‐infrared (NIR) fluorescence (FL) imaging with photoacoustic (PA) imaging offers a powerful approach, as the 2D FL data can validate and supplement the 3D PA information for a more holistic disease assessment. Herein, we developed CS‐CO , an activatable dual‐mode NIR probe for the selective monitoring of CO fluctuations in HF. Density functional theory (DFT) calculations validated the design, elucidating the signal turn‐on mechanism upon CO binding. The metal‐free CS‐CO probe selectively detects CO, resulting in activated NIR absorption (710 nm) and emission (742 nm). Consequently, its excellent NIR PA and FL performance allowed for visualizing both exogenous and endogenous CO in cells, and for 2D FL and 3D PA imaging in mice. Crucially, using this dual‐mode imaging approach, CS‐CO successfully revealed dynamic CO level changes during both HF progression and drug‐induced reversal for the first time. This study provides a pioneering strategy for early HF diagnosis and drug efficacy evaluation, with significant potential clinical impact.
He et al. (Fri,) studied this question.