Lipid Droplet-Specific Fluorescent Probe for In Vivo Visualization of Polarity in Fatty Liver, Inflammation, and Cancer Models

Abstract

Elucidating the intrinsic relationship between diseases and lipid droplet (LD) polarity remains a great challenge owing to the lack of the research on multiple disease models. Until now, the visualization of abnormal LD polarity in models of inflammation and clinical cancer patient samples has not been achieved. To meet the urgent challenge, we facilely synthesized a robust LD-specific and polarity-sensitive fluorescent probe (LD-TTP), which consists of a triphenylamine segment as an electron-donor group (D) and a pyridinium as an electron-acceptor moiety (A), forming a typical D−π−A molecular configuration. Owing to the unique intramolecular charge transfer effect, LD-TTP exhibits high sensitivity to polarity change in the linear range from Δf = 0.258 to 0.312, with over 278-fold fluorescence enhancement. Moreover, we revealed that LD-TTP possessed satisfactory ability for sensitively monitoring LDpolarity changes in living cells. Using LD-TTP, we first demonstrated the detection of LD-polarity changes in fatty liver tissues and inflammatory living mice via confocal laser scanning fluorescence imaging. Surprisingly, the visualization of LD polarity has been achieved not only at the cellular levels and living organs but also in surgical specimens from cancer patients, thus holding great potential in the clinical diagnosis of human cancer. All these features render LD-TTP an effective tool for medical diagnosis of LD polarity-related diseases.

Low Polarity-Triggered Basic Hydrolysis of Coumarin as an AND Logic Gate for Broad-Spectrum Cancer Diagnosis

“…Upon decreasing the solvent polarity from Δf ∼ 0.320 to Δf ∼ 0.287 (1,4-dioxane/ water from 0 to 60%, which only change polarity), 1−3 do not show an obvious change in fluorescence; however, 4 displays a significant fluorescence enhancement (Figures S1A−D and S2), which may be because 4 has less charge separation and weak interaction with solvents in low polarity media. 27,28 All probes exhibit no obvious fluorescence response to pH changes in high polarity media (Britton Robinson buffer, BR) (Figure S1A1 S3, the maximum absorption intensity of 1 and 4 decreased slightly during hydrolysis. However, 2 and 3 can only undergo significant hydrolysis at pH = 9 (Figure S4).…”

“…As a result, these molecules are poorly fluorescent as the excited state energy is constantly dissipated through the nonradiative TICT process. Upon decreasing the solvent polarity from Δ f ∼ 0.320 to Δ f ∼ 0.287 (1,4-dioxane/water from 0 to 60%, which only change polarity), 1–3 do not show an obvious change in fluorescence; however, 4 displays a significant fluorescence enhancement (Figures S1A–D and S2), which may be because 4 has less charge separation and weak interaction with solvents in low polarity media. , All probes exhibit no obvious fluorescence response to pH changes in high polarity media (Britton Robinson buffer, BR) (Figure S1A1–D1), and only 1 displays a sensitive fluorescence turn-on response to OH – in low polarity media (BR, pH = 8, 50% dioxane, v/v) (Figure S1A2–D2). Probe 4 shows a fluorescence quenching phenomenon for OH – in a low polarity media, which is due to the hydrolysis of its coumarin fluorescent skeleton.…”

Advances in Optical Imaging of Nonalcoholic Fatty Liver Disease

“…The difference between NAFLD tissue and normal liver tissue can be observed in the green fluorescence channel, fatty liver tissue has been successfully realized the visualization of LDs polarity. [17] 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).…”

Observing hepatic steatosis with a commercially viable two-photon fluorogenic probe

“…The typical method for observing the polarity of hepatic lipid droplets is one-photon confocal microscopy. 21 However, for in vivo biological tissue and mouse imaging, two-photon confocal microscopy has a variety of advantages including near infrared light excited nonlinear optical processes. 22,23 Additionally, commercial fluorophores ( e.g.…”