Light-responsive phase-change nanoparticles for on-demand oxygen release to alleviate hypoxia for wound healing...

Treatment strategies involving reactive oxygen species (ROS), such as chemodynamic and photodynamic therapies, have been explored for various applications, including inflammatory, infection-related, and cardiovascular disorders. However, their efficacy is often limited by hypoxia, which also impacts cellular metabolism and disease progression through hypoxia-inducible factors (HIFs). Here, we report light-responsive nanoparticles (NPs) designed to supply oxygen (O₂) and hydrogen peroxide (H₂O₂) on demand to enhance the effectiveness of ROS- and O₂-dependent therapies. This nanosystem consists of polydopamine (PDA)-coated calcium peroxide (CPO) NPs, whose surface is further modified with lauric acid (LA) (PDA@CPO-LA NPs), a phase-change material with a melting point of ∼44-46 °C. Upon near-infrared (NIR) 808 nm laser irradiation, the photothermal PDA absorbs light and converts it to heat, triggering the phase transition of LA. This transition facilitates water penetration and decomposition of the covered CPO, releasing H₂O₂ and O₂ on demand. The generated H₂O₂ is subsequently converted to O₂ by catalase (CAT), which further helps mitigate O₂ deprivation, as demonstrated with 3T3-L1 fibroblasts. In vivo biosafety of the light-responsive NPs was confirmed using the Galleria mellonella larval model, showing no systemic, digestive, or contact toxicity upon exposure. The findings underscore the potential of NIR-activated NPs as a controllable and biocompatible platform for enhancing ROS- and O₂-based therapeutic modalities.