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
- signaling pathway
- diabetic rats
- reactive oxygen species
- ischemia reperfusion injury
- cancer therapy
- simultaneous determination
- anti inflammatory
- gene expression
- photodynamic therapy
- cell death
- liver failure
- small molecule
- drug delivery
- heat shock
- dna methylation
- bone marrow
- intensive care unit
- genome wide identification
- heat shock protein
- respiratory failure
- endoplasmic reticulum stress
- extracorporeal membrane oxygenation
- high resolution
- climate change
- tandem mass spectrometry
- replacement therapy