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

Abstract

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.

Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging

“…To shift the chemiluminescence towards a relatively biological transparent near‐infrared (NIR) region, chemiluminescent substrates have been doped into nanoparticles to construct resonance energy transfer [25–29] . However, such nanoparticle approach can potentially reduce chemiluminescent brightness as a result of extra energy relay processes, and the physical entrapment of chemiluminescent substrate significantly prevents its contact with biomolecules, limiting their detection species to small and diffusive molecules such as ROS.…”

Activatable Chemiluminescent Molecular Probes for Bioimaging and Biosensing

“…To prolong the emission wavelength to the NIR‐II region and improve the penetration depth and signal‐to‐noise ratio (SNR) of in vivo imaging, Zhang et al . rationally designed a high contrast NIR‐II CLS by cascade CRET (CPPO to BTD540) and FRET (BTD540 to BBTD700) processes [14] . Further result demonstrates that NIR‐II CLS in NIR‐II chemiluminescence imaging enables higher SNR in the inflammation imaging of lymph node and arthrosis region in mice over conventional NIR‐I detection and NIR‐II fluorescence imaging (Figure 9F).…”

“…Y. H. Seo et al ., [74] A. J. Shuhendler et al [30] . and Y. Yang et al [14] . successfully regulated the chemiluminescence emission at 700 nm ( 47 , 48 ), 820 nm ( 45 , 49 ) and 935 nm ( 50 , 51 ) by FRET‐CRET process (Figure 4D).…”

“…Currently, the chemiluminescence acceptors are mainly fluorescent dyes ( 13 – 41 , Figure 4B) and semiconducting polymers ( 42 – 46 , Figure 4C) [14,22,30,38,39,67,71–79] . We summarize the chemiluminescence emission of these acceptors and the limitation of detection (LOD) of H 2 O 2 and calculated their HOMO energy by performing density functional theory (DFT) (Table 1).…”

Molecular Chemiluminescent Probes with a Very Long Near‐Infrared Emission Wavelength for in Vivo Imaging

“…[24] To shift the chemiluminescence towards a relatively biological transparent near-infrared (NIR) region, chemiluminescent substrates have been doped into nanoparticles to construct resonance energy transfer. [25][26][27][28][29] However, such nanoparticle approach can potentially reduce chemiluminescent brightness as a result of extra energy relay processes, and the physical entrapment of chemiluminescent substrate significantly prevents its contact with biomolecules, limiting their detection species to small and diffusive molecules such as ROS. Thus, direct modification of Shaaps dioxetane into NIR chemiluminescence scaffolds is a desired strategy to further improve and broaden the application of chemiluminescence imaging.…”