Core-shell lycopene-loaded nanoparticle-modified intraocular lens for posterior capsule opacification prevention via mitochondrial homeostasis.

Posterior capsule opacification (PCO) develops when residual lens epithelial cells (LECs) proliferate, migrate, and undergo epithelial-mesenchymal transition (EMT) after cataract surgery. Because mitochondrial dysfunction may promote EMT-associated cellular remodeling, modulation of mitochondrial quality control could provide a complementary strategy for PCO prevention. Lycopene (LYC) is a natural antioxidant capable of regulating mitochondrial homeostasis. Here, we developed a microfluidic-engineered LYC-eluting intraocular lens (IOL) modified with poly(lactic-co-glycolic acid) (PLGA)-shelled LYC-loaded liposome-core nanoparticles (LYC@Lip@PLGA-IOL). This dual-encapsulation design improved LYC formulation stability, reduced the initial burst release, and enabled sustained LYC release over a 14-day period in vitro. In SRA01/04 lens epithelial cells, LYC attenuated PI3K/AKT activation, activated mitophagy, restored mitochondrial membrane potential and ATP production, reduced reactive oxygen species (ROS) accumulation, and consequently inhibited EMT and migration. In a rabbit PCO model, LYC@Lip@PLGA-IOL reduced posterior capsule opacity, capsular thickening, and EMT-associated fibrotic remodeling, while exhibiting favorable ocular and systemic biocompatibility over 28 days. These findings support sustained local delivery of LYC as a mitophagy-activating strategy for restoring mitochondrial homeostasis and preventing PCO.