NK cell vesicles-based nanoplatform loaded with sorafenib synergizing ferroptosis and antitumor immunity against hepatocellular carcinoma

BACKGROUND: Ferroptosis is a type of cell death that relies on iron and is marked by an excess of intracellular iron and the buildup of lipid peroxides. This process presents a new and promising approach for cancer treatment. Improving ferroptosis can effectively mitigate the limitations of conventional treatment methods. METHODS: We developed a synergistic nanotherapeutic platform. Natural killer cell derived nanovesicles (NK-NVs) were fabricated using an extrusion method and subsequently loaded with sorafenib (SRB) via electroporation, resulting in the NK-NVs-SRB complex for targeted delivery. RESULTS: The therapeutic strategy not only escaped recognition by drug efflux pumps, thus lowering drug expulsion, but also effectively triggered ferroptosis in cancer cells. This process induced significant release of damage associated molecular patterns (DAMPs), ultimately leading to immunogenic cell death (ICD). In vivo experiments demonstrated that NK-NVs-SRB intervention achieved a tumor growth inhibition rate of 44.54%, effectively drove the ferroptosis process, and activated anti-tumor immunity by recruiting CD8 + T cell infiltration. CONCLUSIONS: This study proposes a novel therapeutic strategy for hepatocellular carcinoma (HCC) that acts by synergistically inducing ferroptosis and activating anti-tumor immunity, thereby paving a new avenue for HCC treatment.