Targeting delivery of anti-TNF  oligonucleotide into activated colonic macrophages protects against experimental colitis

Abstract

It is the first time a non-viral gene vector has been combined with an ASO targeted to activated macrophages in the treatment of CD. The inhibition of TNFalpha by this strategy represents a promising therapeutic approach for the treatment of CD.

Colonic gene silencing using siRNA-loaded calcium phosphate/PLGA nanoparticles ameliorates intestinal inflammation in vivo

“…Therefore, intestinal epithelial cell-based therapeutics are a crucial field of interest for therapy. While previous studies showed a beneficial effect of targeting macrophages with siRNA [61][62][63][64] in our study, we demonstrated that intestinal epithelial cells can be a therapeutic target. Intestinal epithelial cells take up CaP/ PLGA nanoparticles in vitro and in vivo.…”

An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease

“…A more ideal way is to treat the IBD promoting TNF-a in the pathologically functional cells -colonic macrophages. Our previous study suggested that directly intracolonic delivering TNF-a ASO targeting colonic macrophage had significant therapeutic effects on experimental colitis and little influences on the physiological function of the immune system [17]. However, the inconvenience and suffering of enema brought to the patients and the complexity of the operation is a limiting obstacle to its further application.…”

The contributing role of the intestinal microbiota in stressor-induced increases in susceptibility to enteric infection and systemic immunomodulation

“…However, NF-κB activation can also be pathologic; prolonged activation of NF-κB can result in the over-production of inflammatory cytokines like TNF-α (Li and Verma, 2002;Neish, 2004). TNF-α is an integral component of the mucosal immune response to intestinal pathogens, but when produced in excess leads to tissue-damaging colitis (Zuo et al, 2010). This is evident in laboratory animals with experimental colitis, as well as human patients with inflammatory bowel disease (Kaser et al, 2010;Zuo et al, 2010).…”