Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model

• Published in: Advanced healthcare materials 2021-04, Vol.10 (7), p.e2001736-n/a
• Main Authors: Adhikari, Aniruddha, Mondal, Susmita, Das, Monojit, Biswas, Pritam, Pal, Uttam, Darbar, Soumendra, Bhattacharya, Siddhartha Sankar, Pal, Debasish, Saha‐Dasgupta, Tanusri, Das, Anjan Kumar, Mallick, Asim Kumar, Pal, Samir Kumar
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Antioxidants; Biocompatibility; Biocompatible Materials; Cellular communication; Citric acid; Enzymes; functionalized nanoparticles; Glutathione; Glutathione peroxidase; Huntington's disease; Huntingtons disease; Hydrogen peroxide; In vivo methods and tests; Incompatibility; Manganese; Manganese oxides; Metabolic networks; nanomedicine; nano‐enzymes; Neurodegenerative diseases; neurodegenerative disorder; Peroxidase; Physiology; preclinical animal studies; Scavenging; sensitized nanomaterials; Toxicity
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202001736

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, it is shown that citrate functionalized manganese‐based biocompatible nanoscale material (C‐Mn3O4 NP) efficiently mimics glutathione peroxidase (GPx) 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. The in vivo therapeutic efficacy of C‐Mn3O4 nanozyme is further established in a preclinical animal model of Huntington's disease (HD), a prevalent progressive neurodegenerative disorder, which has no effective medication to date. Management of HD in preclinical animal trial using a biocompatible (non‐toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy. Citrate functionalized Mn3O4 nanoparticles can mimic glutathione peroxidase (GPx) to treat Huntington's like severe neurobehavioral toxicity in experimental animals. The nanoparticles are biocompatible, can efficiently function in the physiological milieu, and possess the unique ability to be incorporated into the cellular enzyme cascade. Successful human trials will impart a new regime in treatment of neurodegenerative disorders like Huntington's, Parkinson's, Alzheimer's, etc.