NDLI: The conjugation of Cu/Zn superoxide dismutase (SOD) to O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC) enhances its therapeutic potential against radiation-induced oxidative damage

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The conjugation of Cu/Zn superoxide dismutase (SOD) to O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC) enhances its therapeutic potential against radiation-induced oxidative damage

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Polymer Chemistry Vol - 7 Issue - 8

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The conjugation of Cu/Zn superoxide dismutase (SOD) to O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC) enhances its therapeutic potential against radiation-induced oxidative damage

Content Provider	Royal Society of Chemistry (RSC)
Author	Zhao, Nan Song, Chunxia Liu, Chunhui Xu, Linghua Ji, Xiaohu Wang, Fengshan
Copyright Year	2016
Abstract	A novel polymer–enzyme conjugate, O-HTCC–SOD, was prepared through the conjugation of Cu/Zn superoxide dismutase (SOD) to a macromolecular carrier, O-(2-hydroxyl)propyl-3-trimethyl ammonium chitosan chloride (O-HTCC), by the carbodiimide-mediated coupling method. The resulting O-HTCC–SOD conjugate was characterized by various analytical methods. It was a positively charged polymer with broader molecular weight distribution. Circular dichroism (CD) spectra revealed that the conjugated O-HTCC increased highly ordered secondary motifs of SOD, but also reduced partial β-sheet conformation that is crucial for enzymatic activity, which led to a ∼19% activity loss. O-HTCC–SOD could increase its catalytic activity to a maximum of 2.3-fold through gradual cleavage of O-HTCC linked to SOD by α-amylase. It exhibited low cytotoxicity to cells, and superior membrane permeability to native SOD. The conjugate, alone or incubated with α-amylase, significantly protected cell viability from ionizing radiation-induced oxidative damage by scavenging intracellular reactive oxygen species (ROS). Pharmacokinetic analysis demonstrated that the conjugation of O-HTCC to SOD prolonged its half-life 8.2-fold and increased its bioavailability to 1.56-fold after a single intravenous administration compared to native SOD, and that the time to maximum serum concentration (Tmax) of O-HTCC–SOD was 50-fold longer than that of native SOD, suggesting unique sustained activity enhancement in vivo presumably triggered by biodegradability of O-HTCC. We finally investigated its therapeutic effect against ROS-induced damage induced by whole-body X-ray radiation in mice. O-HTCC–SOD remarkably attenuated ROS-induced oxidative damage and induced tissue protection in mice whereas native SOD failed to do so. Therefore, the biodegradable cationic chitosan derivative O-HTCC can serve as a carrier to improve the therapeutic potential of SOD. The O-HTCC–SOD conjugate might be a promising therapeutic agent for treatment of ROS-related diseases.
Starting Page	1826
Ending Page	1835
Page Count	10
File Format	HTM / HTML PDF
ISSN	17599954
Volume Number	7
Issue Number	9
Journal	Polymer Chemistry
DOI	10.1039/c5py02025e
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Biodegradation Ammonium Reactive oxygen species Amylase Cell membrane Superoxide dismutase Polymer Cytotoxicity Bioavailability Circular dichroism X-ray crystallography Chloride Biological half-life Chitosan Beta sheet Transport maximum Protein structure
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Bioengineering Biomedical Engineering Polymers and Plastics

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