Journal
JOURNAL OF CONTROLLED RELEASE
Volume 347, Issue -, Pages 544-560Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.05.025
Keywords
Oral nanoparticle; Antimicrobial peptide; Inflammatory microenvironment; Microbial remodeling; Ulcerative colitis
Funding
- National Natural Science Foundation of China [82072060, 31830094, U20A2058]
- Fundamental Research Funds for the Central Universities [XDJK2019TY002]
- Science and Technology Department of Jiangxi Province [20212BDH81019]
- Natural Science Foundation Project of Chongqing [cstc2020jcyj-msxmX0292]
- Venture & Innovation Support Program for Chongqing Overseas Returnees [cx2018029]
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Smart epigallocatechin-3-gallate (EGCG)-loaded silk fibroin-based nanoparticles can restore colonic epithelial barriers, relieve oxidative stress, promote epithelial migration, alleviate immune responses, and eliminate lipopolysaccharides (LPS) in ulcerative colitis (UC). Oral administration can modulate intestinal microbiota and increase the abundance of beneficial bacteria.
The pathogenesis of ulcerative colitis (UC) is associated with severe inflammation, damaged colonic barriers, increased oxidative stress, and intestinal dysbiosis. The majority of current medications strive to alleviate inflammation but fail to target additional disease pathologies. Addressing multiple symptoms using a single 'magic bullet' remains a challenge. To overcome this, a smart epigallocatechin-3-gallate (EGCG)-loaded silk fibroin-based nanoparticle (NP) with the surface functionalization of antimicrobial peptides (Cathelicidin-BF, CBF) was constructed, which could be internalized by Colon-26 cells and RAW 264.7 macrophages with high efficiencies. The resulting CBF-EGCG-NPs efficiently restored colonic epithelial barriers by relieving oxidative stress and promoting epithelium migration. They also alleviated immune responses through downregulation of pro-inflammatory factors, upregulation of anti-inflammatory factors, M2 macrophage polarization, and lipopolysaccharide (LPS) elimination. Interestingly, oral administration of hydrogel (chitosan/alginate)-embedding CBF-EGCG-NPs could not only retard progression and treat UC, but also modulate intestinal microbiota by increasing their overall diversity and richness and augmenting the abundance of beneficial bacteria (e.g., Firmicutes and Lactobacillaceae). Our work provides a many birds with one stone strategy for addressing UC symptoms using a single NP-based oral platform that targets immune microenvironment modulation, LPS clearance, and microbial remodeling.
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