A ratiometric hypochlorite-specific nanoprobe constructed by rationally designed AIE luminogen for fluorescence imaging of alcoholic liver disease

Abstract

There is a lack of effective and friendly diagnostic technique for alcoholic liver disease (ALD). Fluorescence imaging, which has been widely applied in disease diagnostic ascribed to the merits of high sensitivity, excellent temporal resolution and minimal invasiveness, is probably a good candidate for ALD studying. Herein, by precise molecular optimization, an aggregation-induced emission (AIE) probe of TCPQ was designed to show bright near-infrared (NIR) emission centered at 680 nm, and selective response towards ClO− for ALD diagnosis. In comparison with PNQ, the started fluorophore constructed with ClO− oxidizable donor phenothiazine (PZ) and AIE active acceptor quinoline-malononitrile (QM), the emission wavelength and fluorescence quantum yield of TCPQ were 63 nm red-shifted and 2.3-fold enhanced after structural optimization. Once exposed to ClO−, the S atom in PZ donor of TCPQ could be oxidized to sulfoxide, leading to blue-shifted emission, which made TCPQ be suitable for ratiometirc imaging with high accuracy, while the such weak emissions of the other probes here in presence of ClO− made the ratiometric imaging impossible. After forming nanoparticles (NPs) with amphiphilic F-127, TCPQ NPs have successfully imaged the exogenous and endogenous ClO− fluctuations through the ratio between brightness of green channel and red channel, and have been further utilized to quantitatively evaluate the ClO− levels in four types of cells. The possibility of ClO− as a biomarker for ALD was confirmed in the cellular ALD model. Subsequently, TCPQ NPs were further applied in ALD diagnosis and pharmacodynamic evaluation of an anti-ALD drug in the mouse model.