Macrophage and mitochondrion dual-targeting astaxanthin nanoparticles prepared by Maillard reaction for colonic inflammation alleviation

This study demonstrated the design of whey protein isolate (WPI)-mannose (Man) conjugates with triphenylphosphonium bromide (TPP) through self-assembly to prepare macrophage and mitochondrion dual-targeting astaxanthin (AXT) nanoparticles (AXT@TPP-WPI-Man). The nanoparticles displayed spherical structures with a well-dispersed size of approximately 206.1 ± 39.2 nm, with good biocompatibility, stability, and targeting capabilities. In vitro experiments demonstrated the specific accumulation of AXT@TPP-WPI-Man in mitochondria and exhibited good targeting ability toward macrophages. The AXT@TPP-WPI-Man effectively reduced reactive oxygen species and preserved the normal mitochondrial membrane potential. The AXT@TPP-WPI-Man treated ulcerative colitis mice exhibited a 52.32% increase in colon length with significant improvement in weight loss, disease activity index scores, and reduced release of inflammatory cytokines. Immunofluorescence staining indicated AXT@TPP-WPI-Man alleviated ulcerative colitis by reducing M1 polarization in colonic macrophages while promoting M2 polarization. The dual-targeting AXT@TPP-WPI-Man has the potential to improve astaxanthin bioavailability, presenting a promising delivery method for the treatment of ulcerative colitis.