Targeted modulation of intestinal epithelial regeneration and immune response in ulcerative colitis using dual-targeting bilirubin nanoparticles.
Theranostics
; 14(2): 528-546, 2024.
Article
in En
| MEDLINE
| ID: mdl-38169633
ABSTRACT
Rationale The therapeutic benefits of bilirubin in the treatment of ulcerative colitis (UC) are considerable, whereas the underlying mechanism of bilirubin on UC remains unclear remains unexplored. In addition, the weak hydrophilicity and toxicity have limited its translational applications. Methods:
We have developed a colon dual-targeting nanoparticle, for orally delivering bilirubin through hydrogel encapsulation of hyaluronic acid (HA)-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles (HA-PLGABilirubin). Confocal microscopy and in vivo imaging were used to evaluate the uptake and the targeted property of HA-PLGABilirubin in UC. Immunohistochemistry, immunofluorescence, and transcriptomic analyses were applied to examine the therapeutic effect and potential mechanism of HA-PLGABilirubin in UC.Results:
Our results indicated that HA-PLGAbilirubin can significantly enhance the release of bilirubin at simulated intestinal pH and demonstrate higher cellular uptake in inflammatory macrophages. Moreover, in vivo biodistribution studies revealed high uptake and retention of HA-PLGAbilirubin in inflamed colon tissue of UC mouse model, resulting in effective recovery of intestinal morphology and barrier function. Importantly, HA-PLGAbilirubin exerted potent therapeutic efficacy against ulcerative colitis through modulating the intestinal epithelial/stem cells regeneration, and the improvement of angiogenesis and inflammation. Furthermore, genome-wide RNA-seq analysis revealed transcriptional reprogramming of immune response genes in colon tissue upon HA-PLGAbilirubin treatment in UC mouse model.Conclusion:
Overall, our work provides an efficient colon targeted drug delivery system to potentiate the treatment of ulcerative colitis via modulating intestinal epithelium regeneration and immune response in ulcerative colitis.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colitis, Ulcerative
/
Colitis
/
Nanoparticles
Limits:
Animals
Language:
En
Journal:
Theranostics
Year:
2024
Document type:
Article
Affiliation country:
China