A Class of Activatable NIR‐II Photoacoustic Dyes for High‐Contrast Bioimaging

Abstract Photoacoustic (PA) imaging is emerging as one of the important non‐invasive imaging techniques in biomedical research. Small molecule‐ second near‐infrared window (NIR‐II) PA dyes combined with imaging data can provide comprehensive and in‐depth in vivo physiological and pathological information. However, the NIR‐II PA dyes usually exhibit “always‐on” properties due to the lack of a readily optically tunable group, which hinders the further applications in vivo. Herein, a novel class of dyes GX have been designed and synthesized as an activatable NIR‐II PA platform, in which the absorption/emission wavelength of GX‐5 extends up to 1082/1360 nm. Importantly, the GX dyes have a strong tissue penetration depth and high‐resolution for the mouse vasculature structures in NIR‐II PA 3D imaging and high signal‐to‐noise ratio in NIR‐II fluorescence (FL) imaging. Furthermore, to demonstrate the applicability of GX dyes, the first NIR‐II PA probe GX‐5‐CO activated by carbon monoxide (CO) was engineered and employed to reveal the enhancement of the CO levels in the hypertensive mice by high‐contrast NIR‐II PA and FL imaging. We expect that many derivatives of GX dyes will be developed to afford versatile NIR‐II PA platforms for designing a wide variety activatable NIR‐II PA probes as biomedical tools.