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Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model
Author(s) -
Adhikari Aniruddha,
Mondal Susmita,
Das Monojit,
Biswas Pritam,
Pal Uttam,
Darbar Soumendra,
Bhattacharya Siddhartha Sankar,
Pal Debasish,
SahaDasgupta Tanusri,
Das Anjan Kumar,
Mallick Asim Kumar,
Pal Samir Kumar
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202001736
Subject(s) - biocompatible material , enzyme , in vivo , antioxidant , huntington's disease , glutathione peroxidase , chemistry , pharmacology , biochemistry , medicine , glutathione , biology , disease , biomedical engineering , pathology , microbiology and biotechnology
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‐Mn 3 O 4 NP) efficiently mimics glutathione peroxidase (GPx) enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H 2 O 2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. The in vivo therapeutic efficacy of C‐Mn 3 O 4 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.