Polyphenol Carrier-Enhanced Curcumin Nanoparticles for Targeted, Synergic Therapy of Inflammatory Bowel Disease: Self-Adaptive Modulation of Mitochondrial Homeostasis and Immune Response.

Inflammatory bowel disease (IBD) is an intractable and recurrent disease, and nowadays there is undiminished enthusiasm in developing multifunctional carriers for orally administrable natural polyphenols to treat the intestinal microenvironment and immune dysregulation. In this study, polyphenol carrier-enhanced curcumin nanoparticles were demonstrated as an efficacious oral therapeutic to self-adaptively regulate the gastrointestinal microenvironment for alleviating IBD. Tannic acid (TA) and curcumin (CUR) were coassembled via an innovative method in which the oligomerized TA was applied as carriers to solubilize a high amount of CUR up to 50 wt %. The coassembled binary TA/CUR nanoparticles (TC NPs) exhibited salient features including acid-resistant but alkali-responsiveness for oral delivery to the colon, reactive oxygen species (ROS) responsiveness for targeting inflamed colon mucosa, and anti-inflammatory capacities. Cell experiments confirmed the mitochondrial-targeted delivery of TC NPs to mediate ROS for ameliorating mitochondrial dysregulation and modulate macrophage polarization for inhibiting pro-inflammatory responses. Compared with 5-ASA, TA, CUR, and TA NPs, a synergic therapeutic efficacy was achieved with TC NPs in DDS-induced colitis models. The present study demonstrated the targeted therapy of IBD with coassembled TA and CUR of the active components in the diets, showing the great potential for orally administrable natural polyphenols in the treatment and even prevention of gastrointestinal diseases.