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Simultaneous Fenton‐like Ion Delivery and Glutathione Depletion by MnO2‐Based Nanoagent to Enhance Chemodynamic Therapy
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2018-03-23 , DOI: 10.1002/anie.201712027
Li-Sen Lin 1, 2 , Jibin Song 1, 2 , Liang Song 1 , Kaimei Ke 1 , Yijing Liu 2 , Zijian Zhou 2 , Zheyu Shen 2 , Juan Li 1 , Zhen Yang 2 , Wei Tang 2 , Gang Niu 2 , Huang-Hao Yang 1 , Xiaoyuan Chen 2
Affiliation  

Chemodynamic therapy (CDT) utilizes iron‐initiated Fenton chemistry to destroy tumor cells by converting endogenous H2O2 into the highly toxic hydroxyl radical (.OH). There is a paucity of Fenton‐like metal‐based CDT agents. Intracellular glutathione (GSH) with .OH scavenging ability greatly reduces CDT efficacy. A self‐reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.

中文翻译:

基于MnO2的纳米剂同时进行Fenton样离子传递和谷胱甘肽耗竭,以增强化学动力学治疗

Chemodynamic疗法(CDT)利用铁发起芬顿化学通过转换为破坏肿瘤细胞的内源性ħ 2 ö 2到高毒性羟基自由基( OH)。很少有类似Fenton的金属基CDT剂。细胞内谷胱甘肽(GSH)与OH清除能力大大降低了CDT功效。据报道,一种基于MnO 2的自增强CDT纳米剂具有Fenton样Mn 2+传递和GSH耗尽特性。在HCO存在3 - ,这是在生理介质中丰富,锰2+施加芬顿样活性产生来自H 2 O的OH2。癌细胞摄取被MnO 2包覆的中孔二氧化硅纳米颗粒(MS @ MnO 2 NPs)后,MnO 2壳与GSH发生氧化还原反应,形成谷胱甘肽二硫化物和Mn 2+,从而导致GSH耗竭增强的CDT。这与GSH激活的MRI对比作用和MnO 2的解离一起,使MS @ MnO 2 NPs可以实现MRI监测的化学-化学动力学联合治疗。
更新日期:2018-03-23
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