Longevity & AgingDual Ferroptosis Strategy Dismantles Liver Cancer's Immune Shield in Mice
Researchers engineered biomimetic nanoparticles (Sv@PM-M2p) that simultaneously deliver sorafenib (SF) and the FSP1 inhibitor viFSP1 to hepatocellular carcinoma (HCC) cells and immunosuppressive M2 tumor-associated macrophages (TAMs). By blocking both GPX4 and FSP1 — two independent ferroptosis defense pathways — the nanoplatform triggers lipid peroxide accumulation and ferroptotic death in both cell types. This dual action releases immunostimulatory damage signals, promotes dendritic cell maturation and CD8+ T cell infiltration, and remodels the tumor microenvironment from immunosuppressive to immunostimulatory. Combined with anti-PD-L1 antibody therapy, the approach suppressed tumor growth, metastasis, and recurrence across multiple preclinical HCC mouse models, including immune-humanized patient-derived xenografts from etiologically distinct HCCs.
