Electron Transfer based Ultra-bright Organic Afterglow Nanoprobe for Accurate Molecular Imaging in Mice

Abstract Afterglow luminescence can greatly improve the signal-to-background ratio (SBR) of molecule imaging in living animal owing to the no need of real-time light excitation. However, the relatively low luminescence of afterglow nanoprobe and attenuation of maximum intensity (afterglow photobleaching) usually lead to the insufficient sensitivity and the inaccurate quantification for repeated molecular imaging. Furthermore, the requirement of high power of light excitation (up to 1 W/cm 2 ) may result in the inevitable phototoxicity, and the long acquisition time (up to 1 min) make it difficult to detect the rapid biological events. Herein, we design electron-rich trianthracene derivatives (TA)-based organic afterglow nanoparticles (TA-NPs) for high-sensitive, safe, lossless and longitudinal molecular imaging. Notably, a great enhancement of afterglow luminescence performance over the previous reported afterglow nanoparticles is achieved though electron transfer engineering (Table 1): Specifically, TA-NPs can be excited by room light with ultra-low power (58 µW/cm 2 ) and with ultra-short acquisition time (0.01 s). The luminescent intensity of TA-NPs is ~ 500-fold of commonly used organic MEHPPV-based nanoparticles. Negligible afterglow photobleaching in mice is observed even after re-excitation for more than 15 cycles. Such ultra-bright afterglow enables the deep-tissue imaging (up to 6.0 cm) and the ultra-fast afterglow imaging of freely-moving mice in waken state. Moreover, TA-NPs can dynamically and accurately visualize subcutaneous tumor, orthotopic glioma and distinguish the plaque in carotid atherosclerosis. Finally, we develop an afterglow nanoprobe (TA-BHQ), activated only in the presence of Granzyme B, for tracking the time-sensitive Granzyme B activity as a direct way to monitor immunotherapeutic responses.