Near-Infrared\nUnimolecular Chemiluminescence Probes\nfor Deep-Tissue Imaging

Chemiluminescence (CL) imaging has emerged as a promising\noptical\nimaging technique due to minimal background autofluorescence and being\nexcitation-free. However, the emission of most chemiluminescent probes\nwas concentrated in the visible light region, which limited the tissue\npenetration. Although some NIR chemiluminescence probes have been\nreported based on the chemiluminescence resonance energy transfer\n(CRET) strategy, the energy loss was inevitable. Thus, it is crucial\nto develop near-infrared (NIR) unimolecular probes with direct chemiluminescence.\nHerein, we propose a strategy of increasing conjugation for designing\nand synthesizing novel NIR chemiluminescence unimolecular probes that\nconsist of luminol, electron acceptor, π-bridge, and electron\ndonor. Luminol was conjugated\nto the unimolecular backbone to produce direct NIR chemiluminescence.\nNotably, the direct CL mechanism of probes was investigated. Compared\nwith CRET-based chemiluminescence, this direct CL was more advantageous\nto immediately convert the chemical energy into chemiluminescence,\navoiding energy degradation. Furthermore, the corresponding nanoparticles\nwith great biosafety were prepared by self-assembly with amphiphilic\nDSPE-PEG. Especially, TTBL@PEG-NPs with NIR-I emission were successfully\nused in the sensitive in vivo chemiluminescence imaging of various\ninflammation models, such as peritonitis, ear swelling, and colitis.\nThis study paves the way for the design of NIR unimolecular chemiluminescence\nprobes and deep-tissue imaging.