Oxidative stress caused by the overproduction of reactive oxygen species (ROS) plays an important role in inflammatory bowel disease (IBD). It is well-known that the Nrf2-ARE (antioxidative response element) pathway is important in the regulation mechanism of antioxidant defense. Therefore, Nrf2 activation may be an effective therapeutic strategy for IBD. Here, we reported the development of a nucleus-targeted Nrf2 delivery nanoplatform, termed N/LC, that could accumulate in inflamed colonic epithelium, reduce inflammatory responses, and restore epithelium barriers in a murine model of acute colitis. N/LC nanocomposites could quickly escape from lysosomes, so Nrf2 largely accumulated in the nucleus of colonic cells, activated the Nrf2-ARE signaling pathway, further elevated the expression levels of downstream detoxification and antioxidant genes, and protected cells from oxidative damage. These results suggested that N/LC might be a potential nanoplatform for IBD therapy. The study provided the basis for the biomedical applications of Nrf2-based therapeutics in various diseases.
Keyphrases
- oxidative stress
- induced apoptosis
- dna damage
- ulcerative colitis
- diabetic rats
- signaling pathway
- reactive oxygen species
- ischemia reperfusion injury
- cancer therapy
- simultaneous determination
- mass spectrometry
- gene expression
- stem cells
- photodynamic therapy
- small molecule
- liver failure
- heat shock
- poor prognosis
- intensive care unit
- mesenchymal stem cells
- human health
- long non coding rna
- genome wide
- liquid chromatography
- high resolution
- endoplasmic reticulum stress
- risk assessment
- bone marrow
- drug delivery
- dna methylation
- drug release
- tandem mass spectrometry