An exosome-biomimetic photothermal nanocarrier for IGF2BP2 siRNA delivery and enhanced ferroptosis in head and neck squamous cell carcinoma - PubMed
6 hours ago
- #Photothermal therapy
- #Ferroptosis
- #Gene therapy
- Head and neck squamous cell carcinoma (HNSCC) often develops treatment resistance, necessitating new therapeutic strategies.
- Ferroptosis is a promising therapeutic route, but its regulatory determinants in HNSCC are not well understood.
- The RNA-binding protein IGF2BP2 promotes ferroptosis resistance by increasing NRF2 mRNA stability and sustaining the NRF2-SLC7A11/GPX4 antioxidant axis.
- A biomimetic hybrid nanocarrier (si@PLE) was engineered by fusing M1 macrophage-derived exosomes with photothermally responsive cationic liposomes for targeted IGF2BP2 siRNA delivery.
- si@PLE showed improved siRNA protection, tumor accumulation, and enhanced tumor-site heating under irradiation compared to non-fused controls.
- In vitro and in vivo, si@PLE combined with near-infrared laser irradiation enhanced ferroptosis and significantly suppressed tumor growth with a favorable safety profile.
- The study establishes a biomimetic gene silencing-photothermal platform to sensitize HNSCC to ferroptosis by targeting the IGF2BP2-NRF2 axis.