Abstract

Oxidative stress in periodontitis has emerged as one of the greatest barriers to periodontal tissue restoration. In this study, we synthesized controlled drug release nanoparticles (MitoQ@PssL NPs) by encasing mitoquinone (MitoQ; an autophagy enhancer) into tailor-made reactive oxygen species (ROS)-cleavable amphiphilic polymer nanoparticles (PssL NPs) to regulate the periodontitis microenvironment. Once exposed to reactive oxygen species, which were substantially overproduced under oxidative stress conditions, the ROS-cleavable PssL was disintegrated, promoting the release of the encapsulated MitoQ. The released mitoquinone efficiently induced mitophagy through the PINK1-Parkin pathway and successfully reduced oxidative stress by decreasing the amount of reactive oxygen species. With the gradual decrease in the reactive oxygen species level, which was insufficient to disintegrate PssL, the release of mitoquinone was reduced and eventually eliminated, which contributed to a redox homeostasis condition and facilitated the regeneration of periodontal tissue. MitoQ@PssL NPs have great potential in the treatment of periodontitis via microenvironment-controlled drug release, which will provide a new avenue for periodontal regeneration and diseases related to imbalanced redox metabolism.