"Dual-Key-and-Lock" NIR-II NSCyanines Enable High-Contrast Activatable Phototheranostics in Extrahepatic Diseases.

Conventional cyanine dyes with a symmetric structure are "always-on", which can easily accumulate in the liver and display high liver background fluorescence, inevitably interfering the accurate diagnosis and therapy in extrahepatic diseases. We herein report a platform of NIR-II non-symmetric cyanine (NSCyanine) dyes by harnessing a non-symmetric strategy, which are extremely sensitive to pH/viscosity and can be activated via a "dual-key-and-lock" strategy. These NSCyanine dyes with a low pKa (<4.0) only show weak fluorescence at lysosome pH (key1), however, the fluorescence can be completely switched on and significantly enhanced by intracellular viscosity (key2) in disease tissues, exhibiting high target-to-liver ratios up to 19.5/1. Notably, high-contrast phototheranostics in extrahepatic diseases are achieved, including intestinal metastasis-imaging, acute gastritis-imaging, bacteria infected wound healing, and tumor ablation via targeted combined photothermal therapy and chemotherapy.

An Activatable Probe with Aggregation-Induced Emission for Detecting and Imaging Herbal Medicine Induced Liver Injury with Optoacoustic Imaging and NIR-II Fluorescence Imaging.

Whilte herbal medicines are widely used for health promotion and therapy for chronic conditions, inappropriate use of them may cause adverse effects like liver injury, and accurately evaluating their hepatotoxicity is of great significance for public health. Herein, an activatable probe QY-N for diagnosing herbal-medicine-induced liver injury by detecting hepatic NO with NIR-II fluorescence and multispectral optoacoustic tomography (MSOT) imaging is demonstrated. The probe includes a bismethoxyphenyl-amine-containing dihydroxanthene serving as electron donor, a quinolinium as electron acceptor, and a butylamine as recognition group and fluorescence quencher. The hepatic level of NO reacts with butylamine, thereby generating the activated probe QY-NO which exhibits a red-shifted absorption band (700-850 nm) for optoacoustic imaging and generates strong emission (910-1110 nm) for NIR-II fluorescence imaging. QY-NO is aggregation-induced-emission (AIE) active, which ensures strong emission in aggregated state. QY-N is utilized in the triptolide-induced liver injury mouse model, and experimental results demonstrate the QY-N can be activated by hepatic NO and thus be used in detecting herbal-medicine-induced liver injury. The temporal and spatial information provided by three-dimensional MSOT images well delineates the site and size of liver injury. Moreover, QY-N has also been employed to monitor rehabilitation of liver injury during treatment process.