CD44-targeted therapy using mP6/Rg3 micelles inhibits oral cancer stem cell proliferation and migration

BACKGROUND: This study investigates how mP6/Rg3 micelles modulate ABCB1 expression to induce ferroptosis in oral cancer stem cells (CSC) and enhance oral cancer outcomes. METHODS: Micelles targeting CD44 peptide P6 were prepared and characterized using TEM and immunofluorescence. Biocompatibility was evaluated through LIVE/DEAD staining and CCK-8 assays. Impact on oral cancer CSC was assessed through in vitro and OSCC mouse model studies using transcriptomic profiling, proteomic analysis, and metabolomic screening. RESULTS: mP6/Rg3 micelles exhibited good biodegradability, inhibiting CSC proliferation and migration. Integrated multi-omics analysis highlighted ABCB1 as a pivotal modulator in OSCC. Functional assays in cell and animal models validated micelles promote ferroptosis in CSC by inhibiting ABCB1, improving OSCC pathology. CONCLUSIONS: Targeting ABCB1 with mP6/Rg3 micelles and regulating CD44 presents a promising approach to suppress oral cancer progression by impacting CSC and tumor metabolic pathways. This study offers crucial molecular insights for new therapeutic strategies in oral cancer treatment.