Preclinical study demonstrates that a gas-generating nanoplatform enhances ferroptosis and extends survival in tumor-bearing mice, indicating a potent multimodal approach to cancer therapy.
Key Points
To develop an engineered nanoplatform combining nitric oxide gas therapy with glutathione depletion to overcome antioxidant defenses and trigger ferroptosis in tumors.
Engineered the MIL-100@Era/L-Arg-HA nanoplatform integrating iron metal-organic frameworks, erastin, and L-arginine.
Evaluated iron valence changes, nitric oxide generation, glutathione depletion, GPX4 inactivation, and lipid reactive oxygen species accumulation in vitro.
Assessed anti-tumor growth inhibition and survival prolongation in tumor-bearing mice in vivo.
MIL-100@Era/L-Arg-HA effectively depleted intracellular glutathione via multiple pathways, inactivated GPX4, and markedly elevated lipid reactive oxygen species levels in vitro.
Treatment significantly inhibited tumor progression and prolonged overall survival times in tumor-bearing mice in vivo.