Extracellular Fenton-like reaction via glucose oxidase-loaded nanocapsule to Fe3O4 nanoparticle cascades enables enhanced cancer cell killing

초록

Fenton-like reactions have attracted considerable attention for cancer therapy due to their ability to generate cytotoxic hydroxyl radicals. However, conventional approaches requiring intracellular delivery face challenges including high antioxidant defense systems and complex nanoparticle modifications. Here, we propose an extracellular Fenton-like reaction system utilizing glucose oxidase-loaded silica nanocapsules (GOX@SiNCs) and Fe3O4 nanoparticles. GOX@SiNCs were synthesized via inverse miniemulsion-based sol-gel reaction and PEGylated to prevent cellular internalization. The encapsulated GOX maintained stable activity against proteolytic degradation. The cascade system successfully generated hydroxyl radicals through GOX-produced H2O2 and Fe3O4-catalyzed Fenton-like reaction. Notably, gluconic acid byproduct lowered extracellular pH, enhancing Fenton-like catalytic efficiency up to 1.4-fold at pH 6.8. Cell viability studies confirmed enhanced cytotoxicity when both nanoparticle systems were combined compared to GOX@SiNCs alone. This extracellular approach bypasses intracellular antioxidant barriers and simplifies nanoparticle design, offering a practical strategy for reactive oxygen species-mediated cancer therapy.

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