Inhibition of Transmural Inflammation in Crohn's Disease by Orally Administered Tumor Necrosis Factor-Alpha Deoxyribozymes-Loaded Pyroptosis Nanoinhibitors.
ACS Appl Mater Interfaces
; 16(31): 40499-40514, 2024 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-39051468
ABSTRACT
Crohn's disease (CD) is a refractory chronic inflammatory bowel disease (IBD) with unknown etiology. Transmural inflammation, involving the intestine and mesentery, represents a characteristic pathological feature of CD and serves as a critical contributor to its intractability. Here, this study describes an oral pyroptosis nanoinhibitor loaded with tumor necrosis factor-α (TNF-α) deoxyribozymes (DNAzymes) (DNAzymes@degradable silicon nanoparticles@Mannose, Dz@MDSN), which can target macrophages at the site of inflammation and respond to reactive oxygen species (ROS) to release drugs. Dz@MDSN can not only break the inflammatory cycle in macrophages by degrading TNF-α mRNA but also reduce the production of ROS mainly from macrophages. Moreover, Dz@MDSN inhibits excessive pyroptosis in epithelial cells through ROS clearance, thereby repairing the intestinal barrier and reducing the translocation of intestinal bacteria to the mesentery. Consequently, these combined actions synergistically contribute to the suppression of inflammation within both the intestine and the mesentery. This study likely represents the first successful attempt in the field of utilizing nanomaterials to achieve transmural healing for CD, which also provides a promising treatment strategy for CD patients.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Crohn
/
Fator de Necrose Tumoral alfa
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DNA Catalítico
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Piroptose
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
ACS Appl Mater Interfaces
Assunto da revista:
BIOTECNOLOGIA
/
ENGENHARIA BIOMEDICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China