Plant-derived extracellular vesicles, Light, Reactive oxygen species (ROS), Encapsulation, Photosensitizing properties, Lipid peroxidation, Materials of engineering and construction. Mechanics of materials, TA401-492

Abstract Plant-derived extracellular vesicles (PDEVs) have emerged as innovative nanocarriers for drug delivery, offering advantages such as biocompatibility, stability, and cost-effectiveness. This study explores light-mediated strategies to optimize cargo encapsulation into PDEVs while preserving structural integrity. Leveraging the intrinsic photosensitizing properties of PDEVs, light irradiation (LED) triggered reactive oxygen species (ROS) generation, including superoxide anions and singlet oxygen, which transiently enhanced membrane permeability for controlled drug loading. Using FITC-dextran (70 kDa) as a model cargo, we optimized light-induced loading efficiency, achieving a peak (~ 80%) at 10 min of irradiation. Prolonged exposure (15 min) reduced efficiency (~ 50%), likely due to excessive ROS-induced membrane destabilization. The optimal PDEVs-to-cargo ratio (1:30) ensured maximal loading while maintaining stability over 30 days. Lipid peroxidation analysis further confirmed ROS-induced membrane modifications through malondialdehyde (MDA) accumulation. These findings demonstrate that PLDENs (Pueraria lobate-derived exosomes-like nanovesicles) function as light-responsive nanocarriers, balancing ROS-mediated permeability enhancement with structural integrity. This light-triggered strategy balances permeability modulation and structural integrity, advancing PDEVs as scalable, non-invasive platforms for precision drug delivery and photodynamic applications.