Scheme 1

An overview of this study: We used high-throughput sequencing to identify the key factor that regulates the metastasis of oral squamous cell carcinoma (OSCC), LCN2, and revealed that LCN2 promotes the metastatic regulation of OSCC through EGFR activation and recycling. We designed and used glutathione-responsive PEG-SS-PLGA nanoparticles (NPs) containing encapsulated siLCN2. The NPs enter tumor tissue through the EPR effect and are taken up by tumor cells. Through lysosomal escape and the intracellular glutathione response, the NPs release siLCN2, which effectively downregulates the protein expression of LCN2 in tumors and inhibits the EGFR/MEK/ERK signaling pathway. Ultimately, the metastatic function of OSCC cells is inhibited