Multifunctional liposome boosts glioma ferroptosis and immunotherapy through reinforcement of chemo-dynamic therapy strategy

Glioma remains significant challenging to completely cure by the conventional surgical resection because of its high infiltrative growth properties. Recently, emerging immunotherapy has achieved remarkable success in treating various cancer, but glioma do not benefit from cancer immunotherapy owing to its specific immunosuppressive tumor microenvironment (iTME). Herein, we show the significant improvement of the immunotherapy efficacy for glioma through multifunctional liposome (Lpo@Cu₂Se-GOx). After tumor cells endocytosis, the released glucose oxidase (GOx) could oxidize glucose into gluconic acid to achieve starvation therapy and generate H₂O₂ as byproduct. Meanwhile, these properties might further cause anti-oxidant systems dysfunction and reinforce Cu²⁺ based Fenton-like reaction, which lead to lipid peroxides accumulation and ferroptosis occur. Moreover, the onset of ferroptosis would trigger the release of damage-associated molecular patterns and induce immunogenic cell death, which contributed to the dendritic cell maturation and cytotoxic T cell infiltration. Besides, in vitro and in vivo experiments verified that Lpo@Cu₂Se-GOx had well significant glioma inhibition without adverse reactions. Taken together, our research demonstrates the modulation of iTME through self-amplified chemo-dynamic therapy could be a significant strategy to improve the immunotherapy of glioma.