α-Tocopherol-loaded reactive oxygen species-scavenging ferrocene nanocapsules with high antioxidant efficacy for wound healing.

The elevated production of reactive oxygen species (ROS) in wounded sites triggers a series of harmful effects, including cellular senescence, fibrotic scar formation, and inflammation. Therefore, alleviating oxidative stress in the microenvironment of wounded sites might promote regenerative wound healing. Generally, ROS-scavenging nanocapsules are effective for treating wounds owing to their anti-oxidative stress activity and targeted effects. In this study, a highly versatile ferrocene functional polymer was synthesized by one-pot radical polymerization, for formulating self-assembled ferrocene nanocapsules (FNCs), which could function as smart carriers of an antioxidant, α-tocopherol (TP), with high stability and loading efficiency. The FNCs showed ROS-sensitive properties, as demonstrated using dynamic light scattering, transmission electron microscopy, and the controlled release of a model drug in an ROS microenvironment. The antioxidant activity of TP-loaded FNCs, analyzed using 2,2-diphenyl-1-picrylhydrazyl assay, was significantly higher than that of unloaded TP. Furthermore, TP-loaded FNCs repressed oxidative damage to mouse NIH 3T3 fibroblasts and reduced intracellular ROS production according to an in vitro antioxidant assay. Most importantly, TP-loaded FNCs showed good biocompatibility and greatly facilitated the healing of infected wounds, as demonstrated using a scratch assay. Therefore, TP-loaded FNCs have potential as an ROS-mediated drug delivery system to treat various oxidative stress-associated diseases.