NIR‐II Chemiluminescence Molecular Sensor for In‐Vivo High Contrast Inflammation Imaging

Chemiluminescence (CL) sensing without the external excitation ligh t and autofluorescence interference has been applied to high-contrast in vitro immunoassays and in vivo inflammation and tumor microenvironment detection. However, conventional CL sensing usually operates in the range of 400-850 nm, which limits the high-performance of in vivo imaging due to the serious light scattering effect and signals attenuation in tissue. To address this challenge, here we present a new type of CL sensor in the second near-infrared window (NIR-II CLS) with deep penetration depth (~ 8 mm) by employing successive CL resonance energy transfer (CRET) and Forster resonance energy transfer (FRET) from the activated CL substrate to two rationally designed donor-acceptor-donor fluorophores BTD540 and BBTD700. NIR-II CLS can be selectively activated by hydrogen peroxide over other reactive oxygen species (ROSs). Moreover, NIR-II CLS is capable of detecting local inflammation in mice with 4.5-fold higher signal-to-noise ratio (SNR) than that under NIR-II fluorescence modality.