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

作     者：Fanwen Sun Yayun Peng Yanping Li Menghan Xu Ting Cai Fanwen Sun;Yayun Peng;Yanping Li;Menghan Xu;Ting Cai

作者机构：State Key Laboratory of Natural MedicinesDepartment of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China 

出 版 物：《Chinese Chemical Letters》 (中国化学快报（英文版）)

年 卷 期：2023年第34卷第2期

页      面：376-381页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 0703[理学-化学] 10[医学] 

基　　金：financial support of this work by the National Natural Science Foundation of China (No. 81872813) the Outstanding Youth Fund of Jiangsu Province of China (No. BK20190029) the China Postdoctoral Science Foundation (No. 2021M703597) the Program of State Key Laboratory of Natural Medicines-China Pharmaceutical University (No. SKLNMZZ202031)。 

主　　题：Acetaminophen Metal-organic framework Fenton reaction Cancer therapy Nanocomposite 

摘      要：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.