An NIR Fluorescent Probe for Real-Time Polarity Sensing and Targeted Lipid Droplet Imaging in Aging, Cancer, and Fluorescence-Guided Cancer Surgery

Lipid droplets (LDs) are dynamic organelles that store energy and regulate lipid metabolism and cell signaling. Their dynamic changes are closely associated with pathological conditions such as aging and cancer, making them promising biomarkers and therapeutic targets. Notably, aging and cancer are closely interconnected; however, few molecular probes can simultaneously monitor both processes. In particular, challenges remain in achieving real-time imaging of LDs dynamics under complex pathological conditions, especially in deep tissues. To address these issues, we developed a novel near-infrared (NIR) fluorescent probe, LJ-LD, featuring a donor−π–acceptor structure with strong intramolecular charge transfer (ICT) characteristics. LJ-LD demonstrates ultrahigh selectivity for LDs, high sensitivity to environmental polarity, superior photostability, and low cytotoxicity. Its NIR emission (≥650 nm) significantly reduces biological autofluorescence and enhances the tissue penetration. The detection limit of LJ-LD for LDs reaches 0.276 μg/mL, indicating its high analytical sensitivity. By combining LJ-LD imaging with commercial senescence detection kits, we achieved enhanced accuracy in assessing cellular senescence and the efficacy of antiaging drugs. Furthermore, LJ-LD differentiates tumors from normal tissues based on polarity variations. These features empower LJ-LD to serve as a multifunctional probe for both the diagnosis of aging-related diseases and fluorescence-guided tumor surgery, offering broad potential for applications in disease research, diagnostics, and therapeutics.