Stimulus-Responsive Targeted Lutein Nanoparticles for the Alleviation of Blue Light-Induced Retinal Degeneration

Growing concern about the prolonged exposure to blue light on eye health has driven interest in bioactive substances that can help protect the eyes. In this study, a type of mitochondrion targeted lutein nanoparticles with potential of hydrogen (pH) and reactive oxygen species (ROS)-responsive capabilities was designed and prepared for retinal degeneration caused by blue light. Lutein nanoparticles were initially prepared using a self-assembly method based on (3-carboxypentyl) (triphenyl) phosphonium modified casein-mannose (CAS-Man) conjugates. Subsequently, 3-aminobenzeneboronic acid modified sodium alginate was surrounded on the surface of the nanoparticles to generate hydrophilic corona. The nanoparticles exhibited pH- and ROS-responsive release properties and showed good mitochondrial targeted ability after 4 h of incubation, with a Pearson's correlation coefficient of 0.88. Visual electrophysiology results indicated that lutein nanoparticles alleviated blue light damage by improving dark and light adaptation, preserving retinal vascular microcirculation, and enhancing optic nerve conduction function. Fluorescein fundus angiography showed that lutein nanoparticles significantly decreased the vessel percentage area by 6.93 ± 0.32%, average vessel length by 0.59-fold, and the number of junctions by 0.88-fold caused by blue light exposure. Lutein nanoparticles effectively protected mice from blue light-induced retinal degeneration by reducing ROS production in the retina by 1.44-fold and inhibiting cellular apoptosis by 2.29-fold. These findings suggested that the mitochondrion targeted lutein nanoparticles with pH and ROS-responsive capabilities provided a potential strategy for mitigating blue light-induced retinal degeneration.