Orally ROS/pH Dual‐Responsive and Targeted Fucoxanthin Microspheres for the Alleviation of Colon Inflammation

Abstract Inspired by the excellent antioxidant and anti‐inflammatory effects of fucoxanthin and polyphenols, a pH/ROS dual‐response, dual targeting, and gastric stability fucoxanthin microspheres (SA@CCT@MPN@FX) for the effective mitigation of ulcerative colitis (UC) are developed in present study. Metal‐phenolic nanoparticles formed from epigallocatechin gallate (EGCG) and Fe 3+ are employed as the carrier to encapsulate fucoxanthin, followed by surface coating with chondroitin sulfate modified (5‐carboxypentyl) (triphenyl) phosphonium bromide, and finally coated with sodium alginate. Structural characterization confirms the successful encapsulation of fucoxanthin within uniformly dispersed core–shell nanostructures. The dual‐responsive release characteristics of fucoxanthin in the targeted nanoparticles are observed at low pH and in the presence of 10 × 10 −3 m hydrogen peroxide (H 2 O 2 ) at pH7.4. Meanwhile, the fabricated fucoxanthin targeted nanoparticles shows excellent macrophage and mitochondrial targeting abilities, the SA@CCT@MPN@FX microspheres can substantially alleviate UC by downregulating the expression levels of oxidative stress and inflammatory cytokines, repairing intestinal damage, ameliorating the composition and relative abundance of intestinal microbiota and short‐chain fatty acids levels through the synergistic antioxidant effects of fucoxanthin and EGCG. This study provides a streamlined strategy for constructing dual‐responsive targeted delivery systems as well as highlights the potential of oral hydrophobic bioactive substances for UC intervention.