Citation: Fanwen Sun, Yayun Peng, Yanping Li, Menghan Xu, Ting Cai. Fenton-reaction-triggered metabolism of acetaminophen for enhanced cancer therapy[J]. Chinese Chemical Letters, ;2023, 34(2): 107507. doi: 10.1016/j.cclet.2022.05.021 shu

Fenton-reaction-triggered metabolism of acetaminophen for enhanced cancer therapy

State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China

tcai@cpu.edu.cn

Received Date: 6 January 2022
Revised Date: 29 April 2022
Accepted Date: 10 May 2022
Available Online: 14 May 2022

Figures(4)

Acetaminophen (APAP), a classic nonsteroidal anti-inflammatory drug (NSAID), has attracted much attention due to the overdose-induced hepatotoxicity in the past several decades. N-Acetyl-p-benzoquinone imine (NAPQI), the P450-dependent metabolism of APAP, leads to GSH depletion, protein binding, mitochondrial oxidative stress, and eventually the liver injury. Herein, we develop a Fe-based metal-organic framework (MOF) to deliver and transform acetaminophen into toxic "chemo" drug through the cascade reaction for enhanced cancer therapy. In the acidic tumor microenvironment, the Fe-based MOF collapses and releases abundant Fe ions to generate hydroxyl radicals (^•OH) via Fenton reaction, subsequently catalyzing nontoxic APAP into toxic NAPQI. Meanwhile, NAPQI depletes intracellular glutathione (GSH) rapidly, leading to alleviating the antioxidant ability of cancer cells and amplifying Fenton activity. The intracellular oxidative stress and the toxic metabolite of APAP can provide a synergistic effect on antitumor activity.
- Acetaminophen,
- Metal-organic framework,
- Fenton reaction,
- Cancer therapy,
- Nanocomposite
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