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Copper-thioguanine metallodrug with self-reinforcing circular catalysis for activatable MRI imaging and amplifying specificity of cancer therapy
Science China Chemistry ( IF 10.4 ) Pub Date : 2020-05-15 , DOI: 10.1007/s11426-020-9738-5
Haifeng Yuan , Yan Zhao , Chan Yang , Cheng Zhang , Yue Yang , Hongmin Meng , Shuangyan Huan , Guosheng Song , Xiaobing Zhang

For chemotherapy, drug delivery systems often suffer from the inefficient drug loading capability, which usually cause systems toxicity and extra burden to excrete carrier itself. Moreover, the cancer therapeutic efficacy is also greatly limited by the specificity of tumor microenvironment for reactive oxygen species (ROS) based cancer therapeutic strategy (e.g., chemodynamic therapy). Herein, we have developed metal-drug coordination nanoplatform that can not only be responsive to tumor microenvironment but also modulate it, so as to achieve efficient treatment of cancer. Excitingly, by employing small molecule drug (6-thioguanine) as ligand copper ions, we achieve a high drug loading rate (60.1%) and 100% of utilization of metal-drug coordination nanoplatform (Cu-TG). Interestingly, Cu-TG possessed high-efficiently horseradish peroxidase-like, glutathione peroxidase-like and catalase-like activity. Under the tumor microenvironment, Cu-TG exhibited the self-reinforcing circular catalysis that is able to amplify the cellular oxidative stress, inducing notable cancer cellular apoptosis. Moreover, Cu-TG could be activated with glutathione (GSH) and facilitated for GSH triggered 6-TG release, higher selective therapeutic effect toward cancer cells, and GSH activated T1 weight-magnetic resonance imaging. Based on the above properties, Cu-TG exhibited magnetic resonance imaging (MRI) guiding, efficient and synergistic combination of chemodynamic and chemotherapy with self-reinforcing therapeutic outcomes in vivo.



中文翻译:

具有自增强循环催化作用的铜硫鸟嘌呤金属药物可用于可激活的MRI成像并增强癌症治疗的特异性

对于化学疗法,药物输送系统通常遭受无效的药物装载能力的困扰,这通常导致系统毒性和排泄载体本身的额外负担。此外,癌症治疗功效还受到肿瘤微环境对基于活性氧(ROS)的癌症治疗策略的特异性的极大限制(例如,化学动力疗法)。本文中,我们开发了金属-药物配位纳米平台,该平台不仅可以响应肿瘤微环境,而且可以对其进行调节,从而实现对癌症的有效治疗。令人兴奋的是,通过使用小分子药物(6-硫鸟嘌呤)作为配体铜离子,我们实现了较高的药物负载率(60.1%)和100%的金属-药物配位纳米平台(Cu-TG)利用率。有趣的是,Cu-TG具有类似辣根过氧化物酶,谷胱甘肽过氧化物酶和过氧化氢酶的活性。在肿瘤微环境下,Cu-TG表现出自增强的环状催化作用,能够放大细胞的氧化应激反应,诱导明显的癌细胞凋亡。此外,Cu-TG可以被谷胱甘肽(GSH)激活并促进GSH触发6-TG释放,T 1重量磁共振成像。基于上述特性,Cu-TG在体内表现出了磁共振成像(MRI)指导,化学动力学和化学疗法的有效和协同结合以及自我增强的治疗效果。

更新日期:2020-05-15
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