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Polymeric DNase-I nanozymes targeting neutrophil extracellular traps for the treatment of bowel inflammation.

Authors :
Wang, Chi-Pin James
Ko, Ga Ryang
Lee, Yun Young
Park, Juwon
Park, Wooram
Park, Tae-Eun
Jin, Yoonhee
Kim, Se-Na
Lee, Jung Seung
Park, Chun Gwon
Source :
Nano Convergence; 2/8/2024, Vol. 11 Issue 1, p1-16, 16p
Publication Year :
2024

Abstract

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a family of chronic disorders along the gastrointestinal tract. Because of its idiopathic nature, IBD does not have a fundamental cure; current available therapies for IBD are limited to prolonged doses of immunomodulatory agents. While these treatments may reduce inflammation, limited therapeutic efficacy, inconsistency across patients, and adverse side effects from aggressive medications remain as major drawbacks. Recently, excessive production and accumulation of neutrophil extracellular traps (NETs) also known as NETosis have been identified to exacerbate inflammatory responses and induce further tissue damage in IBD. Such discovery invited many researchers to investigate NETs as a potential therapeutic target. DNase-I is a natural agent that can effectively destroy NETs and, therefore, potentially reduce NETs-induced inflammations even without the use of aggressive drugs. However, low stability and rapid clearance of DNase-I remain as major limitations for further therapeutic applications. In this research, polymeric nanozymes were fabricated to increase the delivery and therapeutic efficacy of DNase-I. DNase-I was immobilized on the surface of polymeric nanoparticles to maintain its enzymatic properties while extending its activity in the colon. Delivery of DNase-I using this platform allowed enhanced stability and prolonged activity of DNase-I with minimal toxicity. When administered to animal models of IBD, DNase-I nanozymes successfully alleviated various pathophysiological symptoms of IBD. More importantly, DNase-I nanozyme administration successfully attenuated neutrophil infiltration and NETosis in the colon compared to free DNase-I or mesalamine. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
21965404
Volume :
11
Issue :
1
Database :
Complementary Index
Journal :
Nano Convergence
Publication Type :
Academic Journal
Accession number :
175456506
Full Text :
https://doi.org/10.1186/s40580-024-00414-9