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

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 Fe³⁺ 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 (H₂O₂) 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.