Exploiting the Twisted Intramolecular Charge Transfer Effect to Construct a Wash-Free Solvatochromic Fluorescent Lipid Droplet Probe for Fatty Liver Disease Diagnosis

Abstract

The prominent pathological feature of fatty liver disease lesions is excessive fat accumulation in lipid droplets in hepatocytes. Thus, developing fluorescent lipid droplet-specific probes with high permeability and a high imaging contrast provides a robust tool for diagnosing fatty liver diseases. Herein, we rationally developed a novel donor−acceptor lipophilic fluorescent probe ANI with high photostability for wash-free visualization of lipid droplets and fatty liver disease characteristics. ANI showed a typical twisted intramolecular charge transfer effect with very faint fluorescence in high-polar solvents, but dramatically boosted emissions in low-polar environments. The solvatochromic probe can selectively light up lipid droplets with a high contrast in a wash-free manner. Further use of ANI to reveal the excessive accumulation of lipid droplets with a significantly large size in the liver tissues from the fatty liver disease model mice was successfully demonstrated. The remarkable imaging performances rendered ANI an alternative tool for accurately evaluating fatty liver disease in intraoperative diagnosis.

Advances in Optical Imaging of Nonalcoholic Fatty Liver Disease

“…It has been reported that changes in peroxisome polarity are closely related to the occurrence and development of NAFLD, showing great potential for the diagnosis biomarker of NAFLD. [21] Given that, Tang et al designed a polarity-sensitive two-photon fluorescent probe 5 (PX-P, Figure 4A) for targeting peroxisomes, which revealed a decrease in the peroxisomal polarity in a high-fat diet (HFD)-induced NAFLD (Figure 4B) by fluorescence imaging in cells, liver tissues and in vivo, as well as [18] Copyright © 2022, American Chemical Society. Fluorescence imaging enables monitoring of decreased peroxisome polarity in the liver of NAFLD mice.…”

“…In addition to triphenylamine as a polarity‐sensitive group, Niu et al . constructed a solvatochromic fluorescent probe 3 ( ANI , Figure 2A) with a twisted intramolecular charge transfer (TICT) effect by introducing a strongly electron‐withdrawing 1,3‐indanedione unit into the dimethylamino group‐substituted naphthalene skeleton [18] . Further imaging of liver tissue from guinea pigs with high‐fat feeding successfully suggested excessive accumulation of large LDs in liver tissue with the potential for the occurrence of NAFLD (Figure 2B).…”

“… (A) The structure and reaction mechanism of probe 3 to detect polarity. (B) Fluorescence images of normal and high‐fat‐fed guinea pig liver tissues [18] . Copyright © 2022, American Chemical Society .…”

Triphenylamine indanedione as an AIE-based molecular sensor with one-step facile synthesis toward viscosity detection of liquids

“…35,36 Based on their excellent properties in photochemistry and photophysics, they have been commonly used in the construction of chemical sensors. 37,38 Inspired by previous findings and continuous interest in viscosity determination, the molecular sensors DPBID and DPTMID were constructed with the triphenylamine donor (D) and indanedione acceptor (A), while the sensor DPTMID was designed by linking the conjugated thiophene with upon D and A groups, which formed into the flexible D-π-A chemical structure. Both molecular sensors exhibit quenching state in low-viscosity medium due to the free intramolecular rotation, whereas in high viscosity medium, intramolecular motions are inhibited, leading to a turn-on signal, as displayed in Scheme 1.…”

Highly Efficient Luminescence from Charge-Transfer Gold Nanoclusters Enabled by Lewis Acid

“…Intramolecular charge transfer (ICT), namely, charge transfer from the electron-rich part to conjugated electron-deficient one in a molecule, can alter molecule structure and electron distribution. − The occurrence of ICT commonly generates two drastically different states, i.e., local excited (LE) state and the ICT state. − Precisely controlling the proportion of LE and ICT states in the excited process will endow organic molecules and inorganic–organic complexes with tunable luminescence. − Such a unique feature is appealing for their subsequent applications in sensing, biological imaging, and optical switches. − However, the rational design of ICT-based fluorescence probes in aqueous solution remains a serious challenge because the flexible intramolecular rotation in a polar solvent favors nonradiative decay and greatly weakens ICT emission . In recent years, the restriction of intramolecular motion (RIM) has been demonstrated to be a promising approach to strengthen the emission from the ICT state owing to its ability to significantly suppress the ultrafast nonradiative relaxation following an ICT process. , Unfortunately, this strategy usually suffers from some typical problems, such as producing large size of architectures with poor water-solubility and involving a cumbersome modification procedure …”