Mitochondria-targeted drug delivery system based on tetrahedral framework nucleic acids for bone regeneration under oxidative stress

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Oxidative stress is present in many diseases and severely affects tissue reconstruction and regeneration. Many traditional Chinese medicinal monomers have excellent antioxidant effects; however, most cannot target the mitochondria, where oxidative stress is produced. In this study, a mitochondria-targeted antioxidant delivery system based on tetrahedral framework nucleic acids (tFNAs) is developed to combat oxidative stress. Antioxidant quercetin cargoes can be effectively loaded into the tFNA “trucks”, and the trucks are modified with mitochondria-targeting molecules to act as “headlights” to efficiently transport the cargo to the mitochondria. These results confirm that the delivery system can be efficiently loaded with quercetin and target the mitochondria. Both in vitro and in vivo studies confirm that the delivery system resists oxidative stress and inflammatory responses in a diabetic periodontitis model, which suffers from severe oxidative stress. The constructed delivery system delays the destruction of periodontal tissues, and promotes periodontal tissue regeneration. This study provides a new strategy for the efficient and targeted delivery of antioxidants, which is of great significance for the therapy of oxidative stress-related diseases and tissue regeneration.