TY - JOUR
T1 - Bioorthogonal conjugation and responsive nanocoating of probiotics for inflammatory bowel disease
AU - Peng, Pandi
AU - Feng, Tao
AU - Yang, Xue
AU - Ding, Rui
AU - Wang, Junru
AU - Chen, Pengyu
AU - Guo, Yuxin
AU - Li, Peng
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/10
Y1 - 2024/10
N2 - Inflammatory bowel disease (IBD) is closely associated with dysregulated immune response, gut mucosal barrier, and microbiota. Conventional treatments suffer from inferior bioavailability and inadequate efficiency. Herein, we present a synergistic therapeutic strategy based on multifunctionalized probiotics to mitigate IBD through single oral administration. The probiotic (Escherichia coli Nissle 1917) is bioorthogonally conjugated with immunomodulators and subsequently encapsulated by an enteric coating. The viability and bioactivity of probiotics are not affected by the modifications. And the armored probiotics are able to resist the harsh environment of the stomach and shed their enteric coating in the intestinal tract, exposing immunomodulators to polarize pro-inflammatory M1-type macrophages into anti-inflammatory M2-type. In a mouse colitis model, orally administered multifunctionalized probiotics cooperatively alleviate IBD with increased body weight to 1.13 folds and decreased disease activity index to 0.43 folds, through downregulating the pro-inflammatory cytokines expression, upregulating the epithelial tight junction-associated proteins levels to restore the intestinal barrier, and increasing the microbiota richness and abundance. This work exhibits a feasible approach to construct functionalized orally administered probiotics for enhanced synergistic therapy of IBD.
AB - Inflammatory bowel disease (IBD) is closely associated with dysregulated immune response, gut mucosal barrier, and microbiota. Conventional treatments suffer from inferior bioavailability and inadequate efficiency. Herein, we present a synergistic therapeutic strategy based on multifunctionalized probiotics to mitigate IBD through single oral administration. The probiotic (Escherichia coli Nissle 1917) is bioorthogonally conjugated with immunomodulators and subsequently encapsulated by an enteric coating. The viability and bioactivity of probiotics are not affected by the modifications. And the armored probiotics are able to resist the harsh environment of the stomach and shed their enteric coating in the intestinal tract, exposing immunomodulators to polarize pro-inflammatory M1-type macrophages into anti-inflammatory M2-type. In a mouse colitis model, orally administered multifunctionalized probiotics cooperatively alleviate IBD with increased body weight to 1.13 folds and decreased disease activity index to 0.43 folds, through downregulating the pro-inflammatory cytokines expression, upregulating the epithelial tight junction-associated proteins levels to restore the intestinal barrier, and increasing the microbiota richness and abundance. This work exhibits a feasible approach to construct functionalized orally administered probiotics for enhanced synergistic therapy of IBD.
KW - Bioorthogonal conjugation
KW - Gut microbiota
KW - Inflammatory bowel disease
KW - Probiotics
UR - http://www.scopus.com/inward/record.url?scp=85202345396&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2024.08.036
DO - 10.1016/j.jconrel.2024.08.036
M3 - 文章
C2 - 39186984
AN - SCOPUS:85202345396
SN - 0168-3659
VL - 374
SP - 538
EP - 549
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -