A lipid droplet-specific fluorescent probe for acute liver injury and tumor diagnosis via aberrant polarity changes

Abstract

A biological microenvironment is characterized by its complexity and variability, with alterations in lipid droplet (LDs) polarity being strongly linked to multiple pathological conditions such as acute liver injury. Thus, assessing the polarity of LDs holds particular significance in diagnosing conditions related to LD polarity. Here, we rationally designed a novel polarity-sensitive and LD-targeting fluorescent probe, TPALD, which incorporates triphenylamine as an electron-donating group and quinoxalinone as an electron-accepting group, establishing an intramolecular charge transfer mechanism. This probe exhibited pronounced solvatochromic behavior, exhibiting distinct fluorescence emission color changes (from green to red) and significant spectral shifts (Δλ = 72 nm) across solvents with varying polarity, indicating exceptional sensitivity to polarity changes (R² = 0.9937 for polarity correlation). Additionally, intracellular imaging experiments revealed that TPALD has low cytotoxicity and exceptional LD-targeted performance. More significantly, TPALD demonstrated the capability to detect polarity fluctuations in both OA-stimulated cells and APAP-induced acute liver injury (ALI) model mice. This capability highlights its substantial potential for early-stage diagnosis of ALI tissue, thereby underscoring its prospective value in future diagnostic applications and biological research pertaining to related diseases.