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

Abstract

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-Mn₃ O₄ NP) efficiently mimics glutathione peroxidase (GPx) enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H₂ O₂ scavenging. A detailed computational study reveals the mechanism of the nanozyme action. The in vivo therapeutic efficacy of C-Mn₃ O₄ 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.

Keywords: Huntington's disease; functionalized nanoparticles; nano-enzymes; nanomedicine; neurodegenerative disorder; preclinical animal studies; sensitized nanomaterials.