A Self-Deliverable H2O2-Responsive Tocopherol Dimer for Enhanced Antioxidant and Liposomal Delivery

Oxidative stress induced by excessive hydrogen peroxide (H2O2) is a critical pathological factor in skin aging, inflammatory disorders, and photodamage. While tocopherol (TCP) is a gold-standard antioxidant in cosmetics, its potential in H2O2-responsive systems remains underexplored. In this study, we report the design and characterization of ditocopheryl peroxalate (TOT), a novel tocopherol dimer linked via a H2O2-cleavable peroxalate linkage. TOT remains chemically stable under physiological conditions but undergoes selective chemiluminescence-like degradation upon exposure to H2O2, simultaneously scavenging H2O2 and liberating two TCP molecules. Notably, TOT demonstrated superior H2O2-scavenging efficiency and enhanced antioxidant and anti-inflammatory effects in H2O2-stimulated cells compared to monomeric TCP, while maintaining excellent biocompatibility. Structural analysis revealed that the rigid, linear configuration of TOT facilitates seamless integration into dipalmitoylphosphatidylcholine (DPPC) bilayers, yielding highly stable H2O2-responsive liposomes. These findings highlight TOT as a sophisticated multifunctional antioxidant platform for advanced cosmeceutical applications targeting photo-induced oxidative damage.