Hematite-embedded mesoporous nanoparticles for ferroptosis-inducing cancer sonoimmunotherapy

Sonodynamic therapy (SDT) aims to treat cancers by generating reactive oxygen species in response to ultrasound (US). However, the clinical applications of SDT are often constrained due to its limited efficacy in triggering systemic immune responses. Considering this, we developed hematite-embedded PEGylated mesoporous silica nanoparticles (H@PMSNs) as potential sonosensitizers for inducing immunogenic cancer cell death. When B16F10 cells were exposed to H@PMSNs under US irradiation, the intracellular levels of glutathione and glutathione peroxidase 4 were significantly reduced, leading to lipid peroxidation of the cell membrane and triggering ferroptosis. Notably, after their systemic administration into tumor-bearing mice, H@PMSNs effectively inhibited tumor growth under US irradiation by inducing ferroptosis. This process led to the enhanced maturation of dendritic cells and a significant increase in cytotoxic T cells. Consequently, the antitumor efficacy of immune checkpoint blockade was significantly enhanced by H@PMSN-based SDT. The results of this study indicate that H@PMSNs, which induce the immunogenic death of cancer cells through hematite-mediated ferroptosis, could be promising sonosensitizers for cancer immunotherapy.