Molecular probes enabling high signal-to-background ratio (SBR) and tissue penetration depth is of great significance to improve the sensitivity and accuracy of in vivo imaging. Afterglow luminescence probes (also called persistent luminescence probes), which can trap excitation energy in defects and slowly release photons after cessation of light excitation, have recently emerged as promising tools for improved the SBR and tissue penetration depth due to the ability to overcome the background interference of biological tissues. Recently, Deju Ye 's group in the School of Chemistry and Chemical Engineering, Nanjing University has collaborated with Takanori Suzuki, an organic professor in the Department of Chemistry of Hokkaido University. By engineering an organic π-electron structure-based electrochromic material (EM 12+) into an H2S-responsive chromophore, they first build H2S-activatable NIR fluorescent probes for noninvasive imaging of H2S in living mice (J. Am. Chem. Soc. 2018, 140, 16340). On the basis of this work, they further optimized the structure of EM 12+ into EM F12+, which shows longer absorption wavelengths and a more positive reduction potential, thus allowing for improved quenching efficacy against NIR light and enhanced reaction kinetics toward H2S. By doping it into a semiconducting polymer nanoparticle (i.e., MEH-PPV), they synthesized a hepatic-tumor-targeting and H2S-activatable NIR afterglow probe (F12+-ANP) (Figure 1). F12+-ANP displays a fast reaction rate (1563 ± 141 M-1 s-1) and large afterglow turn-on ratio (~122-fold) toward H2S, enabling fast quantification of H2S concentration in bloods from healthy persons, hepatic or colorectal cancer patients within 1 min. Following systemic administration, F12+-ANP can offer high SBR to detect s.c. and orthotopic liver tumors, and can also accurately delineate tumor margins in excised hepatic cancer specimens(Figure 2). The H2S-activatable afterglow probe has high biocompatibility, which will be useful for clinical blood tests, in vivo detection of tumor lesion and imaging-guided tumor surgery.
This work has been recently published in Nat. Commun.,2020, 11, 446 (H2S-Activatable Near-infrared Afterglow Luminescent Probes for Sensitive Molecular Imaging in vivo. DOI: doi.org/10.1038/s41467-020-14307-y). The work is supported from t the National Key R&D Program of China (2017YFA0701301), National Natural Science Foundation of China (21922406, 21775071 and 21632008), Natural Science Foundation of Jiangsu Province (BK20190055), the Fundamental Research Funds for the Central Universities (020514380185), Excellent Research Program of Nanjing University (ZYJH004), CAS Key Laboratory of Receptor Research (SIMM1904YKF-03), and Grant-in-aid for Scientific Research on Innovation Areas “Middle molecular strategy from MEXT (Japan).
Figure 1.Schematic illustration of the design, synthesis of F12+-ANP and proposed mechanism of H2S-mediated fast activation of NIR afterglow luminescence at 780 nm following pre-irradiation with an 808-nm laser.
Figure 2. Afterglow imaging of liver tumor tissues in in clinically excised liver specimens using F12+-ANP-Gal.