ArticleTheranostics2026
Glutathione depletion under hypoxia via a birnessite-type manganese oxide nanozyme inducing immunogenic ferroptosis for magnetic resonance imaging guided cancer therapy.
Article in Theranostics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Glutathione (GSH) depletion can inhibit glutathione peroxidase 4 (GPX4) activity, leading to the accumulation of lipid peroxides and the induction of ferroptosis. However, achieving efficient GSH depletion under the hypoxic conditions typical of tumor microenvironments using non-precious metal-based materials remains a significant challenge for effective cancer therapy. Methods: We synthesized a two-dimensional birnessite-type nanosheet-like manganese oxide nanozyme (CMO). The multienzymatic activity and GSH consumption capacity of CMO were evaluated. Density functional theory calculations and material characterizations were utilized to investigate the mechanism of GSH oxidation under varying oxygen levels. Results: CMO demonstrated ultrafast GSH depletion, consuming GSH within 1 minute at a concentration of 20 μg/mL. Importantly, this rapid depletion capacity was not suppressed under hypoxic conditions. Theoretical and experimental analyses revealed that GSH oxidation was driven by the reduction of Mn and the sacrificing of lattice oxygen, which generated oxygen vacancies and a rougher material surface. Conclusions: The study presents a non-precious metal-based birnessite-type manganese oxide nanozyme capable of ultrafast GSH consumption under hypoxia. This platform effectively activates immunogenic ferroptosis and offers strong potential for magnetic resonance imaging-guided cancer immunotherapy.
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