Polydopamine Nanodots Ameliorate Inflammatory Bowel Disease by Restoring Redox Homeostasis and Intestinal Microenvironment.

Abstract

Efficient elimination of intestinal reactive oxygen species (ROS) and accelerated alleviation of proinflammatory microenvironment are considered as a direct approach for the management of inflammatory bowel disease (IBD). Although promising, current treatments focusing on the intestinal inflammation resolution are still unsatisfactory and far from their practical applications. To address these limitations, novel polydopamine nanodots (PDA NDs) are rationally designed and developed as an efficient oral formulation for the targeted IBD treatment by regulating intestinal oxidative stress and proinflammatory microenvironment. Because of their intrinsic chemical structure, PDA NDs not only show high stability in the harsh gastrointestinal environment but also allow the precise targeting accumulation around the inflamed colon, suggesting a significant improvement in the oral therapeutic efficacy. After establishing murine models with different degrees of IBDs, oral administration of PDA NDs to diseased mice can well eliminate excessive oxidative stress, alleviate intestinal inflammation, ameliorate intestinal barrier integrity, as well as rebalance gut microflora. Furthermore, orally delivered PDA NDs exhibit high safety and extremely low toxicity in murine model, providing enough confidence for the further development of targeted IBD treatments. Overall, the current study has proposed a safe, facile, and highly efficient therapeutic strategy for the comprehensive management of IBDs.