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Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model
bioRxiv - Pharmacology and Toxicology Pub Date : 2020-09-25 , DOI: 10.1101/2020.09.23.310995
Aniruddha Adhikari , Susmita Mondal , Monojit Das , Pritam Biswas , Uttam Pal , Soumendra Darbar , Siddhartha Sankar Bhattacharya , Debasis Pal , Tanusri Saha-Dasgupta , Anjan Kumar Das , Asim Kumar Mallick , Samir Kumar Pal

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3O4 NP) efficiently mimics glutathione peroxidase enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. We further established the in vivo therapeutic efficacy of C-Mn3O4 nanozyme in a preclinical animal model of Huntington's disease, a prevalent progressive neurodegenerative disorder, which has no effective medication till date.

中文翻译:

在细胞抗氧化剂酶级联中掺入生物相容性纳米酶可以逆转临床前模型中的亨廷顿病样疾病

纳米酶在治疗用途中的潜力已经指导了当代研究,以开发天然酶的替代品,该天然酶遭受许多缺点,包括稳定性低,成本高和难以储存。然而,固有的毒性,生理环境的低效率以及在细胞酶网络中功能的不相容性限制了纳米酶在生命系统中的治疗用途。在这里,我们已经表明,柠檬酸盐官能化的锰基生物相容性纳米级材料(C-Mn3O4 NP)有效地模仿了生理环境中的谷胱甘肽过氧化物酶,并且可以轻松地掺入细胞多酶级联反应中以清除H2O2。详细的计算研究揭示了纳米酶作用的机理。
更新日期:2020-09-25
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