Photo-enhanced upcycling H<sub>2</sub>O<sub>2</sub> into hydroxyl radicals by IR780-embedded Fe<sub>3</sub>O<sub>4</sub>@MIL-100 for intense nanocatalytic tumor therapy.

Cun, Ju-E; Pan, Yang; Zhang, Zhuangzhuang; Lu, Yao; Li, Junhua; Pan, Qingqing; Gao, Wenxia; Luo, Kui et al. · Biomaterials · 2022

basic_science · Level V

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Abstract

Reactive oxygen species (ROS)-based nanocatalytic tumor therapy is alluring owing to the capability to generate highly cytotoxic ∙OH radicals from tumoral H<sub>2</sub>O<sub>2</sub>. However, the antitumor efficacy is highly dependent on the radical generation efficiency and challenged by the high levels of antioxidative glutathione (GSH) in cancer cells. Herein, we report an IR-780 decorated, GSH-depleting Fe<sub>3</sub>O<sub>4</sub>@MIL-100 (IFM) nanocomposite for photo-enhanced tumor catalytic therapy by extensive production of ∙OH, which is realized by an integration of excellent peroxidase-like activity of IFM, selective upregulation of tumoral H<sub>2</sub>O<sub>2</sub> by β-lapachone, and localized hyperthermia by near infrared light irradiation. IFM shows potentiated antiproliferative effect in 4T1 cancer cells by ∙OH overproduction and glutathione scavenging, inducing intracellular redox dyshomeostasis and cell death by concurrent apoptosis and ferroptosis. In vivo antitumor investigation further demonstrates photoacoustic and fluorescence imaging-guided combinational therapy with a tumor inhibition rate of 96.4%. This study provides a strategy of photo-enhanced nanocatalytic tumor therapy by tumor-specific H<sub>2</sub>O<sub>2</sub> amplification and hyperthermia.