Citation: Zhang Liuwei, Chen Qixian, Wang Jingyun. Advances in Reactive Oxygen Species Responsive Anti-cancer Prodrugs[J]. Acta Chimica Sinica, ;2020, 78(7): 642-656. doi: 10.6023/A20040116 shu

Advances in Reactive Oxygen Species Responsive Anti-cancer Prodrugs

  • Corresponding author: Chen Qixian, qixian@dlut.edu.cn Wang Jingyun, wangjingyun67@dlut.edu.cn
  • Received Date: 24 April 2020
    Available Online: 8 June 2020

    Fund Project: Talent Project of Revitalizing Liaoning XLYC1807184Project supported by the National Natural Science Foundation of China (No. 21878041) and Talent Project of Revitalizing Liaoning (XLYC1807184)National Natural Science Foundation of China 21878041

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  • Reactive oxygen species (ROS) are categorized as a class of instantaneous intermediate products of oxygen, which are usually produced by a single electron continuous reduction of O2. Examples include hydrogen peroxide (H2O2), superoxide anion (O2-), hydroxyl radical (HO·), hypochlorite radical (OCl-) and singlet oxygen (1O2). The endogenous ROS arise from three major resources:mitochondrial electron transport chain (Mito-ETC), endoplasmic reticulum (ER) and NADPH oxidase (NOX). The produced ROS play vital roles in physiological functions including modulation of functions of proteins, regulation of cell signaling, mediation of inflammation, and elimination of pathogens. However, the cumulative ROS level in vivo could elicit oxidative stress, which is implicated in a multitude of diseases including cancer, autoimmune diseases, inflammation, cardiovascular diseases, neurodegenerative diseases. This abnormal biochemical alteration in tumors has inspired researchers to exploit the relatively high levels of ROS for development of ROS-responsive prodrug systems. In recent years, ROS-responsive prodrug systems based on a spectrum of ROS-sensitive linkers have been designed and developed with aim of precision tumor therapy. Herein, in this review, we would like to illustrate ROS-sensitive linkers developed to date including arylboronic acid or ester, alkyl thioether or selenide, thioketal, peroxalate ester, aminoacrylate, thiazolidinone and α-ketoamide, and elucidate the underlying molecular oxidation mechanism. Furthermore, the design of ROS-responsive prodrugs based on these sensitive linkers and their applications in anti-cancer therapy were reviewed. Additionally, the existing problems and the future research perspectives of prodrug systems were also discussed.
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