Fenton-like nanoparticles capable of H 2 O 2 self-supply and glutathione consumption for chemodynamic and chemotherapy of cancer

• Published in: Biomaterials science 2024-10, Vol.12 (21), p.5534-5546
• Main Authors: He, Yongju, Tian, Xiangjie, Zhang, Meiru, Xu, Hui, Gong, Xiyu, Yang, Binbin, Zhou, Fangfang
• Format: Article
• Language: English
• ISSN: 2047-4830; 2047-4849
• DOI: 10.1039/D4BM00930D

Chemodynamic therapy (CDT) utilizing the Fenton reaction to convert hydrogen peroxide (H O ) into cytotoxic hydroxyl radicals (˙OH) has recently drawn extensive interest in tumor treatment. However, the therapeutic efficiency of CDT often suffers from high concentrations of glutathione (GSH), insufficient endogenous H O and inefficient Fenton activity. Herein, a GSH-depleting and H O self-providing nanosystem that can efficiently load copper ions and doxorubicin (DOX) (MSN-Cu -DOX) to induce enhanced CDT and chemotherapy is proposed. The results show that MSN-Cu -DOX could release Cu and DOX under acidic conditions. Particularly, both the released Cu and Cu in MSN-Cu -DOX are available for ˙OH production a Fenton-like reaction for CDT. Meanwhile, Cu undergoes a reduction to Cu by depleting overexpressed GSH, thereby enhancing CDT. Moreover, the released DOX could not only be used for chemotherapy, but also promote the generation of endogenous H O to improve the efficiency of a Cu-based Fenton-like reaction. Resultantly, this nanosystem featuring Fenton-like activity, GSH consumption, H O self-sufficiency and chemotherapy exhibits a great antitumor effect with a tumor inhibition ratio of 93.05%. Overall, this study provides a promising strategy to enhance CDT for effective tumor therapy.