pH响应/H_(2)O_(2)自供型金属过氧化物在肿瘤化学动力学治疗中的应用  

pH-Responsive/H_(2)O_(2) Self-Supplying Metal Peroxides for Tumor Chemodynamic Therapy

作　　者：高铭英 赵婷婷[1] 姜宇[1] 马佳悦 韩育衡 李妍妍 王霆[1] GAO Mingying;ZHAO Tingting;JIANG Yu;MA Jiayue;HAN Yuheng;LI Yanyan;WANG Ting(College of Chemistry,Chemical Engineering and Resource Utilization,Northeast Forestry University,Harbin 150040,China)

机构地区：[1]东北林业大学化学化工与资源利用学院,黑龙江哈尔滨150040

出　　处：《中国材料进展》2023年第10期779-786,共8页Materials China

基　　金：国家自然科学基金项目(H81901868);中央高校基本科研业务费专项资金项目(2572018BU03)。

摘　　要：基于活性氧自由基的抗肿瘤疗法近些年来得到了人们的广泛关注,主要包含光动力疗法、声动力疗法以及化学动力学疗法。其中,化学动力学疗法无需借助外部能量(光能或超声)和氧气,主要依赖金属催化剂(Fe^(2+)、Cu^(+)等)与H_(2)O_(2)分子发生芬顿或类芬顿反应,即可产生高细胞毒性的羟基自由基(·OH)等强氧化性活性物种,该活性物种可破坏细胞脂质、蛋白质和DNA等生物大分子,引发细胞凋亡,从而达到肿瘤治疗的目的。相比应用于传统化学动力学疗法的纳米材料(Fe_(3)O_(4)、Cu_(2)O等),金属过氧化物材料具有在低pH下响应降解、自供H_(2)O_(2)等特点,在应用于肿瘤化学动力学疗法时展现出巨大的优势,逐渐得到了人们的重视。金属过氧化物材料可以在肿瘤病灶区弱酸微环境下生成H_(2)O_(2)与金属离子,依靠肿瘤病灶区H_(2)O_(2)水平的提高和金属离子过载,或者通过产生的金属离子与H_(2)O_(2)进一步发生芬顿或类芬顿反应生成·OH来杀伤肿瘤细胞,同时某些金属离子也会抑制细胞线粒体电子传递链协同杀死肿瘤细胞,从而提高肿瘤多模式治疗效果。从介绍肿瘤化学动力学疗法的概念和治疗机理入手,总结几种不同金属过氧化物纳米材料应用于肿瘤治疗的反应原理与机制,综述目前国内外所开发的pH响应/H_(2)O_(2)自供型金属过氧化物在肿瘤治疗方面的研究进展,并对其应用前景、发展趋势和挑战进行展望。Antitumor therapies based on reactive oxygen species(including photodynamic,sonodynamic and chemodynamic therapy)have attracted extensive attentions in recent years.Among them,chemodynamic therapy requires no external energy(light or ultrasound)and oxygen,but mainly relies on the Fenton or Fenton-like reaction between metal catalysts(Fe^(2+),Cu^(+),etc.)and hydrogen peroxide molecules to produce highly oxidizing active species(like cytotoxic hydroxyl radical·OH).These active species destroy biological macromolecules(such as cell lipids,proteins and DNA,etc.),and trigger cell apoptosis,thus achieving tumor therapy.Compared with traditional chemodynamic therapy nanomaterials(Fe_(3)O_(4),Cu_(2)O,etc.),metal peroxides-based materials have gradually gained people's attention,and show great potentials for chemodynamic therapy application due to their low pH-responsive degradation and self-providing H_(2)O_(2) features.Metal peroxides materials can generate H_(2)O_(2) and metal ions under slightly acidic tumor microenvironment,and kill tumor cells by increasing H_(2)O_(2) level and overloading intratumoral metal ions,or by further producing·OH via Fenton or Fenton-like reaction between metal ions and H_(2)O_(2).In addition,some metal ions can inhibit mitochondrial electron transport chain to synergistically kill tumor cells,thus improving multimodal therapeutic effect on tumors.In this paper,the concept and treatment mechanism of chemodynamic therapy are first introduced,and the reaction principle and mechanism for several different kinds of metal peroxides nanomaterials are summarized.Then the recent domestic and foreign research progress of pH-responsive/H_(2)O_(2) self-supplying metal peroxides nanomaterials applied for tumor treatments is reviewed.Finally,their application potentials,development trends and possible challenges are prospected.

关 键 词：肿瘤微环境 金属过氧化物 芬顿反应 活性氧自由基 化学动力学疗法 

分 类 号：R318.08[医药卫生—生物医学工程] TB383.1[医药卫生—基础医学]