Donor Modulation of Strong Near-Infrared Lipid-Droplet Probes for in Vivo Diagnosis of Nonalcoholic Fatty Liver Disease

Lipid droplet accumulation is a pathological hallmark
of nonalcoholic
fatty liver disease (NAFLD); however, the utility of current lipid
droplet-targeted fluorescent probes for in vivo diagnosis is hindered
by shallow tissue penetration and strong background autofluorescence.
To overcome these challenges, here, we report three donor–acceptor–acceptor
solvatochromic probes (CTBT-ANPy, PTBT-ANPy, and MOPTBT-ANPy) with
tunable electron-donating groups, enabling near-infrared (NIR) imaging
of lipid droplets and in vivo NAFLD diagnosis. Owing to multiple intramolecular
interactions and restriction of twisted intramolecular charge transfer,
these probes exhibit intense NIR emissions (up to 709 nm, quantum
yield of 34.2%) in low-polarity media. These lipophilic probes display
high lipid-droplet specificity with bright light-up signals and wash-free
capacity. With the aid of NIR-emissive MOPTBT-ANPy, in vivo high-contrast
fluorescent discrimination of NAFLD in a mouse model was successfully
achieved. This study underscores the potential of high-performance
NIR probes for noninvasive accurate NAFLD diagnosis and monitoring.