Glutathione-triggered nanoplatform for chemodynamic/metal-ion therapy

The integration of metal-ion therapy and hydroxyl radical (˙OH)-mediated chemodynamic therapy (CDT) holds great potential for anticancer treatment with high specificity and efficiency. Herein, Ag nanoparticles (Ag NPs) were enveloped with Cu²⁺-based metal-organic frameworks (MOFs) and further decorated with hyaluronic acid (HA) to construct a glutathione (GSH)-activated nanoplatform (Ag@HKU-HA) for specific chemodynamic/metal-ion therapy. The obtained nanoplatform could avoid the premature leakage of Ag in circulation, but realize the release of Ag at the tumor site owing to the degradation of external MOFs triggered by Cu²⁺-reduced glutathione. The generated Cu⁺ could catalyze endogenous H₂O₂ to the highly toxic ˙OH by a Fenton-like reaction. Meanwhile, Ag NPs were oxidized to toxic Ag ions in the tumor environment. As expect, the effect of CDT combined with metal-ion therapy exhibited an excellent inhibition of tumor cells growth. Therefore, this nanoplatform may provide a promising strategy for on-demand site-specific cancer combination treatment.