Accurate diagnosis of early-stage lung cancer by targeting lipid droplets with a two-photon near-infrared fluorescence probe

Clinically, solid nodules with adenocarcinoma (SN-ADC) exhibit faster growth and greater invasiveness than ground-glass nodules with adenocarcinoma (GGN-ADC). Metabolic reprogramming is a critical feature of tumor cells and may facilitate the rapid progression of early-stage lung cancer. Herein, we used laser microdissection to precisely isolate malignant regions from five SN-ADC and six GGN-ADC samples for proteomic analysis. Bioinformatic analysis, western blotting, and electron microscopy conducted in this study revealed a significant upregulation of lipid droplet-associated protein (PLIN2) and marked increase in lipid droplet (LD) accumulation in SN-ADC tissues. Consequently, a novel two-photon near-infrared fluorescence probe was developed to monitor the dynamic changes in LDs in lung cancer cells. Further, experimental validation confirmed the effectiveness of the LD probe (LD-probe) in monitoring the changes in LDs in tumor cells and distinguishing LD differences between tumor and normal tissues. In particular, the probe successfully detected significant differences in LD behavior between SN-ADC and GGN-ADC in early-stage lung cancer. Thus, this study developed a rapid and effective tool for the diagnosis of early-stage lung cancer. The proposed method offers deeper insight into the monitoring of the behavior of LDs in tumor cells, with potential clinical applications.