Ultrabright and Highly Polarity‐Sensitive NIR‐I/NIR‐II Fluorophores for the Tracking of Lipid Droplets and Staging of Fatty Liver Disease

Abstract

Visualizing the progression of fatty liver disease in vivo is of great significance in biomedical research of fatty liver, but hindered by the lack of suitable approaches with deep penetration, high specificity, and real-time observability for fatty liver imaging. Herein, two bright NIR-I/NIR-II fluorophores with D-π-A-π-D structures are designed and synthesized for fatty liver tracking in vivo. Such fluorophores show an ultrahigh quantum yield of 49.2% and 17.3% at the emission maximum of 930 and 975 nm, respectively. Most interestingly, these two fluorophores display ultrasensitive fluorescence response (over 100-fold enhancement) toward the variations of environment polarity. Accordingly, further doping of these fluorophores into amphiphilic organic matrix allows the formation of ultrabright NIR-I/NIR-II fluorescent nanoprobes for high-resolution fluorescence imaging of the vessels. Additionally, with the assistance of such nanoprobes and NIR-II fluorescence imaging, real-time monitoring of heartbeat rate and the respiratory rate, accurate identification, and imaging-guided surgery of the submillimeter scale lymph nodes are successfully realized. Moreover, the as-designed fluorophores show superior performance for indicating lipid droplets (LDs) in living cells. Ultimately, precise monitoring of fatty liver with NIR-I/NIR-II fluorescent LDs probe is first confirmed, demonstrating the possibility for staging fatty liver disease with a contact-free method.

Rational Design of a Near-Infrared Ratiometric Probe with a Large Stokes Shift: Visualization of Polarity Abnormalities in Non-Alcoholic Fatty Liver Model Mice

“…Moreover, the ex vivo ratiometric images revealed that the signal ratio F 710 / F 790 enhanced from 1.14 in the liver of healthy mice to 1.58 in the liver of NAFL mice (Figure S18). All the results indicate that the liver polarity of NAFL mice is lower than that of healthy mice, which was consistent with previous reports in the literature. , Cy-Mp can be used as a potential tool for diagnosing NAFL by tracking the polarity disorder of the liver.…”

“…All the results indicate that the liver polarity of NAFL mice is lower than that of healthy mice, which was consistent with previous reports in the literature. 60,61 Cy-Mp can be used as a potential tool for diagnosing NAFL by tracking the polarity disorder of the liver.…”

An aza-BODIPY-based NIR-II luminogen enables efficient phototheranostics

“…33 Meanwhile, maximum fluorescence emission successfully reached the NIR-II region at 1045 nm, and a large Stokes shift of about 185 nm was also observed. The calculated quantum yield value of CB1 was about 2.3% (reference ICG, Φ f = 13% in DMSO 34 ), which is higher than a number of reported organic NIR-II luminogens (Fig. S8 and Table S1 †), revealing the excellent potential for NIR-II imaging.…”

“…S11, † it was observed that the CB1 NP solution showed a conspicuous concentration-dependent fluorescence enhancement, and the quantum yield in PBS solution was found to be 0.2%. 34 The brightness (ε max Φ f ) of the CB1 NPs was 98 M −1 cm −1 , which was brighter than many other reported organic NIR-II fluorophores in aqueous solutions, such as FBP 1025 (33.3 M −1 cm −1 ) 35 and ICG-PEG 45 (3.1 M −1 cm −1 ), 36 indicating a superior potential for NIR-II bio-imaging applications. Next, the photostability of the CB1 NPs and ICG were compared.…”

Solvatochromic Two-Photon Fluorescent Probe Enables In Situ Lipid Droplet Multidynamics Tracking for Nonalcoholic Fatty Liver and Inflammation Diagnoses

“…Lipid droplets are highly dynamic subcellular organelles with powerful energy storage composed of various neutral lipids surrounded by a phospholipid monolayer and various complete peripheral-related regulatory proteins. − Lipid droplets are involved in lipid storage and metabolism, membrane transport, and protein degradation, which have important influences on the internal environments of organisms. , Abnormalities in the activity or number of lipid droplets are closely related to metabolic diseases, such as atherosclerosis (AS), inflammation, and type II diabetes, and in diagnosing nonalcoholic fatty liver disease (NAFLD). − Given the unique role of lipid droplets, real-time visual monitoring of lipid droplets in living cells and tissues is significant for revealing clinical diagnoses and biological functions.…”