Enhanced natural killer cell anti-tumor activity with nanoparticles mediated ferroptosis and potential therapeutic application in prostate cancer

Ferroptosis provides an opportunity to overcome the cancer cell therapeutic resistance and modulate the immune system. Here an interaction between ferroptosis of cancer cells and natural killer (NK) cells was investigated with a clinical grade iron oxide nanoparticle (ferumoxytol) for potential synergistic anti-cancer effect of ferroptosis and NK cell therapy in prostate cancer. When ferumoxytol mediated ferroptosis of cancer cells was combined with NK cells, the NK cells' cytotoxic function was increased. Observed ferroptosis mediated NK cell activation was also confirmed with IFN-gamma secretion and lytic degranulation. Upregulation of ULBPs, which is one of the ligands for NK cell activating receptor NKG2D, was observed in the co-treatment of ferumoxytol mediated ferroptosis and NK cells. Additionally, HMGB1 and PD-L1 expression of cancer cells were observed in the treatment of ferroptosis + NK cells. Finally, in vivo therapeutic efficacy of ferumoxytol mediated ferroptosis and NK cell therapy was observed with significant tumor volume regression in a prostate cancer mice model. These results suggest that the NK cells' function can be enhanced with ferumoxytol mediated ferroptosis.

Automated summary

This study investigated the interaction between ferroptosis of cancer cells and natural killer (NK) cells, and explored the potential anti-cancer effect of ferroptosis and NK cell therapy in prostate cancer using ferumoxytol, a clinical grade iron oxide nanoparticle. The results showed that ferumoxytol-mediated ferroptosis enhances the cytotoxic function of NK cells and leads to significant tumor regression in a prostate cancer mice model. These findings suggest that ferumoxytol-mediated ferroptosis can enhance the function of NK cells and overcome therapeutic resistance in cancer cells.