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Artificial Metalloenzyme-Based Enzyme Replacement Therapy for the Treatment of Hyperuricemia

机译：基于人工金属酶的酶替代疗法治疗高尿酸血症

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摘要

Enzyme replacement therapy (ERT) holds great potential for treating enzyme deficiency related diseases. However, the enzymic vulnerability and the undesirable toxic side effects have strongly limited its clinical applications. Here a novel artificial metalloenzyme-based ERT with significant self-protection and toxic self-cleaning ability is developed for the treatment of hyperuricemia. The uricase and platinum nanoparticles (PtNPs) are closely confined in the pores of mesoporous silica nanoparticles and encapsulated within a silica defense layer to form a tandem catalytic system. This artificial metalloenzyme keeps a high uric acid (UA) degradation activity, as well as a strong resistance capability toward various insults, such as pH, high temperature, and protease. Besides, the H2O2 produced by UA can be simultaneously eliminated by the PtNPs, resulting in significant improvement on the mammalian cell viability. In vivo studies display prominent therapy effect and no obvious side effects during the treatment of hyperuricemia mice using this artificial metalloenzyme. These results provide new insights into development of efficient and friendly enzyme replacement therapy.
机译：酶替代疗法（ERT）在治疗与酶缺乏相关的疾病方面具有巨大潜力。但是，酶的脆弱性和不良的毒副作用严重限制了其临床应用。在这里，新型的基于人工金属酶的ERT具有显着的自我保护和有毒的自我清洁能力，被开发用于治疗高尿酸血症。尿酸酶和铂纳米颗粒（PtNPs）紧密限制在中孔二氧化硅纳米颗粒的孔中，并封装在二氧化硅防护层中以形成串联催化体系。这种人造金属酶保持较高的尿酸（UA）降解活性，以及​​对各种有害物质（例如pH值，高温和蛋白酶）的强大抵抗能力。此外，UA产生的H2O2可以同时被PtNP消除，从而大大提高了哺乳动物细胞的生存能力。体内研究显示，在使用这种人工金属酶治疗高尿酸血症小鼠期间，治疗效果显着且无明显副作用。这些结果为开发高效，友好的酶替代疗法提供了新的见识。

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  • 来源
    《Advanced Functional Materials》 |2016年第43期|7921-7928|共8页
  • 作者

    Liu Xinping; Zhang Zhijun; Zhang Yan; Guan Yijia; Liu Zhen; Ren Jinsong; Qu Xiaogang;

  • 作者单位

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China|Univ Chinese Acad Sci, Beijing 100039, Peoples R China;

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China|Univ Chinese Acad Sci, Beijing 100039, Peoples R China;

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China|Univ Chinese Acad Sci, Beijing 100039, Peoples R China;

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China|Univ Chinese Acad Sci, Beijing 100039, Peoples R China;

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China;

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China;

    Chinese Acad Sci, Changchun Inst Appl Chem, Biol Chem Lab, Changchun 130022, Jilin, Peoples R China|Chinese Acad Sci, Changchun Inst Appl Chem, Lab Rare Earth Resource Utilizat, Changchun 130022, Jilin, Peoples R China;

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