Cyclic cell-penetrating peptide-engineered ceria nanoparticles for non-invasive alleviation of ultraviolet radiation-induced cataract

Oxidative stress, which results from the accumulation of free radicals, plays a substantial role in cataract formation. Antioxidants have shown promise in mitigating or even preventing this process. However, delivering antioxidants noninvasively to the anterior segment of the eye has been a significant challenge. In this study, we developed ceria nanoparticles modified with cyclic cell-penetrating peptides to overcome the obstruction of the dense corneal barrier on topical drug delivery. Our results demonstrated that modified ceria nanoparticles with cell-penetrating peptides (CPPs) facilitate the opening of tight junctions in human corneal epithelial cells. This characteristic considerably enhances the trans-corneal transport of nanoparticles and improves cellular uptake efficiency, while also contributing to their intracellular enrichment toward mitochondria. Further experiments confirmed that the modified ceria nanoparticles effectively counteracted ferroptosis induced by oxidative stress in lens epithelial cells both in vitro and in vivo, substantially reducing cataract formation. The successful development of ceria nanoparticles modified with cyclic cell-penetrating peptides (cCPPs) opens new avenues for research in cataract prevention and treatment. Additionally, the modified ceria nanoparticles could serve as a noninvasive drug delivery system, which holds remarkable potential for advancing drug delivery in diseases affecting the anterior segment of the eye.