Anthocyanin-sulfated polysaccharide–ovalbumin nanocomplex: Intestinal absorption mechanism and intracellular antioxidant activity in Caco-2 cells

This study investigated intestinal absorption and cellular antioxidant efficacy of anthocyanin (ACN)-loaded ovalbumin (OVA)-carrageenans (ι-, λC)/dextran sulfate (DS) nanocomplexes. Utilizing Caco-2 cells, we assessed endocytic pathways, intracellular trafficking, and delivery efficacy of ternary nanocomplexes. ACN-loaded nanocomplexes could be internalized by cells in a time-, dose-, energy-dependent manner, with macropinocytosis, lipid raft/caveolae, and actin co-mediated endocytosis routes playing pivotal roles. Nanocomplexes inhibited P-glycoprotein efflux of Rhodamine-123, enhancing the apparent permeability of ACN into cells, especially for OVA-ιC-ACN. Transport pathways of ACN-loaded nanocomplexes through Caco-2 monolayers involved different organelles including microtubules, Golgi complexes, endoplasmic reticulum, and lysosomes. Compared to free ACN, nanocomplexes exhibited more efficiency in recovering cellular viability and endogenous antioxidant enzyme activities under oxidative stress. Our findings provide a more comprehensive understanding of internalization, transport mechanisms of protein-polysaccharide-anthocyanin nanocomplexes across epithelial cell monolayers, and provide valuable insights for designing efficient ACN-loaded nanocomplex systems with high transportation efficiency and intestinal absorption.