Cyclic reactions-mediated self-supply of H<sub>2</sub>O<sub>2</sub> and O<sub>2</sub> for cooperative chemodynamic/starvation cancer therapy.

Zhang, Xiaojuan; He, Chuanchuan; Chen, Yan; Chen, Chen; Yan, Ruicong; Fan, Ting; Gai, Yongkang; Yang, Tan et al. · Biomaterials · 2021

basic_science · Level V

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Abstract

Hydroxyl radical (·OH)-mediated chemodynamic therapy (CDT) and glucose oxidase (GOx)-based starvation therapy (ST) are two emerging antitumor strategies, limited by acid/H<sub>2</sub>O<sub>2</sub> deficiency and tumor hypoxia, respectively. Herein, we developed a liposomal nanoplatform co-delivering Fe(OH)<sub>3</sub>-doped CaO<sub>2</sub> nanocomposites and GOx molecules for synergistic CDT/ST with a complementary effect. Based on Fenton reactions initiated by iron ions, CaO<sub>2</sub>-supplied H<sub>2</sub>O<sub>2</sub> could not only generate ·OH for H<sub>2</sub>O<sub>2</sub>-sufficient CDT, but also produce O<sub>2</sub> to promote the catalytic efficiency of GOx under hypoxia. In return, the enhanced ST generated gluconic acid and H<sub>2</sub>O<sub>2</sub>, further amplifying CDT. Through in vitro and in vivo experiments, we demonstrated that such a mutually reinforced modality based on the cyclic Fenton/starvation reactions provided a novel and potent anticancer mechanism for the effective treatment of hypoxic cancers.

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