A General Cyanine‐Based Platform for Designing Robust Dual‐Channel Near‐Infrared Fluorescent and Photoacoustic Probes

Abstract The creation of versatile platforms for developing dual‐channel near‐infrared fluorescent (NIRF) and photoacoustic (PA) probes, especially those engineered to minimize channel crosstalk, is crucial for precise biomarker detection. However, such platforms remain scarce. To bridge this gap, this study introduces an innovative cyanine‐based platform, CySN . The CySN platform showcases remarkable wavelength‐shifting properties, including large fluorescent modality shift (68 nm) and PA modality shift (145 nm) after the decaging reaction. These substantial changes lead to an exceptionally high ratiometric NIRF change of 603‐fold and ratiometric PA change of 261‐fold. Leveraging the CySN platform, dual‐channel NIRF/PA probes have been successfully developed for detecting both small molecule biomarker (H 2 O 2 ) and enzyme biomarker (esterase). These probes demonstrate the ability to detect their targets through dual‐channel NIRF/PA detection with high sensitivity and selectivity in vitro. Furthermore, the probes effectively harness NIRF signals to image target analytes in living cells. Notably, the probes demonstrate the capability to accurately diagnose tumors by detecting tumor markers (H 2 O 2 and esterase), revealing a 3.6 to 7‐fold ratiometric PA enhancement over normal tissue. Therefore, the CySN platform holds the potential to further advance the development of dual‐channel NIRF/PA probes for biomolecule detection in disease diagnosis.