In situ-transition nanozyme triggered by tumor microenvironment boosts synergistic cancer radio-/chemotherapy through disrupting redox homeostasis.
In situ-transition nanozyme triggered by tumor microenvironment boosts synergistic cancer radio-/chemotherapy through disrupting redox homeostasis.
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DOI：
10.1016/j.biomaterials.2022.121620
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发表时间：
2022-06
期刊：
影响因子：
14
通讯作者：
Zhongwen Yuan;Xinxin Liu;Jiabao Ling;Guanning Huang;Jiarun Huang;Xueqiong Zhu;Lizhen He;Tianfeng Che
中科院分区：
文献类型：
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作者：
Zhongwen Yuan;Xinxin Liu;Jiabao Ling;Guanning Huang;Jiarun Huang;Xueqiong Zhu;Lizhen He;Tianfeng Che
破坏肿瘤微环境（TME）中的氧化还原稳态，如过量的H2 O2、谷胱甘肽（GSH）和弱酸性，已被证明是有效的肿瘤治疗策略。本文中，我们构建了TME响应性纳米酶DOX@HMSN/Mn 3 O 4（R），其具有由TME原位触发的可逆Mn 3 +/Mn 2+转换，以扰乱固有的氧化还原稳态并催化活性氧（ROS）的过量产生。此外，这种纳米酶可以与TME中过量的GSH反应以产生GSSG，导致消耗还原剂以抑制ROS清除。密度泛函理论计算进一步证实，纳米酶主要表现出氧化酶样活性，催化O2生成羟基自由基，从而强化了TME中的氧化环境。高能X射线与放疗联合应用，可激发纳米酶外层电子，形成光电子参与类氧化酶酶促反应，从而增强ROS积累，放大放/化疗疗效。
Disrupting redox homeostasis in the tumor microenvironment (TME), like excessive H2O2, glutathione (GSH) and weak acidity, has been proved as an effective tumor therapeutic strategy. Herein, we constructed a TME-responsive nanozyme, DOX@HMSN/Mn3O4(R), with reversible Mn3+/Mn2+transitionin situtriggered by TME to perturb the intrinsic redox homeostasis and catalyze reactive oxygen species (ROS) overproduction. In addition, this nanozyme could react with excess GSH in TME to produce GSSG, resulting in the consumption of reducing agents to suppress ROS clearance. Density functional theory calculations further confirmed that the nanozyme mainly exhibited the oxidase-like activity to catalyze the formation of hydroxyl radicals from O2, thus strengthening the oxidation environment in the TME. Combined with radiotherapy, the high-energy X-ray could excite the outer-layer electrons in the nanozyme, forming photoelectrons that participate in the oxidase-like enzymatic reaction, thus intensifying ROS accumulation and amplifying the radio-/chemotherapeutic efficacy.