Nanoreactor for cascade reaction between SOD and CAT and its tissue regeneration effect

Abstract

Nanoreactors for scavenging reactive oxygen species (ROS), a major factor in inflammatory diseases, can reduce overproduced ROS, and thus can prevent further progress of the diseases or facilitate the regeneration of damaged inflamed tissues. Herein, we designed a pluronic-based nanocarrier loaded with dual antioxidant enzymes present in vivo (superoxide dismutase (SOD) and catalase (CAT)) as a nanoreactor system for the regeneration of inflammatory tissue. The catalytic activity of each enzyme was enhanced by loading it into the nanocarrier. More importantly, the nanocarrier could enhance the cascade reaction between SOD and CAT, which converts the superoxide anion to oxygen. The synergistic anti-inflammatory effect of the nanoreactor based on the cascade reaction was verified in vitro. Furthermore, in an inflammatory bowel disease (IBD) mouse model, the dual enzyme (SOD/CAT)-loaded nanocarrier could result in significantly enhanced tissue regeneration and notably alleviated inflammation activities upon intravenous administration of them compared to other control groups, including single enzyme (SOD or CAT)-loaded nanocarrier and the free mixture of both enzymes without the nanocarrier. Thus, the efficacy of the nanoreactor for the cascade reaction on tissue regeneration in vivo was proved. Accordingly, the nanoreactor could be applied for tissue regeneration therapy against various inflammatory diseases.

Keywords: Enzymes; Inflammatory bowel disease; Nanocarrier; Pluronic; Reactive oxygen species; Regeneration.