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

Chemiluminescence (CL) sensing without external excitation by light 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 performance of in vivo imaging due to serious light scattering effects and signal attenuation in tissue. To address this challenge, a new type of CL sensor is presented that functions in the second near-infrared window (NIR-II CLS) with a deep penetration depth (≈8 mm). Successive CL resonance energy transfer (CRET) and Förster resonance energy transfer (FRET) from the activated CL substrate to two rationally designed donor-acceptor-donor fluorophores BTD540 and BBTD700 occurs. 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 a 4.5-fold higher signal-to-noise ratio (SNR) than that under the NIR-II fluorescence modality.