Orally deliverable lutein nanoparticles as robust ROS scavenger for dry eye disease by targeting Peyer’s patches and mitochondria of ocular cell

The excessive production of reactive oxygen species (ROS) inside mitochondria is a significant factor in the perpetuation of dry eye disease (DED), and it may be a key target for DED treatment. In this work, we designed and prepared orally deliverable lutein nanoparticles formulated with phycocyanin, chitosan modified with triphenylphosphonium (TPP), and yeast β-glucan modified with 3-boronobenzoic acid. These nanoparticles possess dual-targeting abilities for microfold cells in Peyer's patches and ocular cell mitochondria to intervene in DED. Our data demonstrated that the dual-targeted lutein nanoparticles effectively accumulated within Peyer's patches and were endocytosed by resident immune cells. In vitro results demonstrated that dual-targeted lutein nanoparticles showed excellent mitochondrial targeting ability with a Pearson correlation value of 0.86 after incubation for 4 h. In vivo results showed that the accumulation of lutein in mouse eye mitochondria increased by 2.36 times. Furthermore, the dual-targeted lutein nanoparticles alleviated oxidative stress damage of the cornea by reducing ROS levels in the cornea, and reduced corneal inflammation and keratinization, thus alleviating DED. The novel lutein nanoparticles with dual abilities to improve absorption efficiency and target mitochondria can be used as a promising candidate for oral intervention in DED.