Zinc-copper bimetallic organic framework nanosheets for synergistic treatment of vitiligo by inhibiting oxidative stress and promoting melanin production

Vitiligo is a prevalent acquired depigmenting disorder with complex pathogenesis, and current treatments targeting individual mechanisms often yield unsatisfactory results. Herein, a multifunctional Cu-Zn bimetallic organic framework nanosheets (Cu/Zn-TA) with capacities of catalyzing dopamine polymerization, improving tyrosinase (TYR) activity and scavenging reactive oxygen species (ROS), have been developed for the treatment of vitiligo. Zn²⁺ nodes in the nanosheets can act as Lewis acid center to polarize phenolic hydroxyl group in dopamine through Lewis acid-base addition reaction. And combined with Jahn-Teller distortion derived from the introduction of Cu²⁺, dopamine was easily oxidized and polymerized by capturing Zn²⁺ from the nanosheets. Additionally, the Cu-Zn caused synergistic effect can enrich dopamine around the nanosheets through Lewis acid-base coordination, and enhance electrons transfer from the hydroxyl group of dopamine to the dual-core copper center of TYR, leading to the enhancement of TYR activity for oxidizing dopamine to dopachrome. Moreover, Cu/Zn-TA nanosheets exhibited multienzyme activities for scavenging various ROS, owing to the Cu²⁺/Cu⁺ redox cycle and the coordination between terephthalic acid (TA) molecules and Zn²⁺. Benefiting from the synergy of multiple therapy mechanisms, Cu/Zn-TA nanosheets can effectively treat vitiligo in a H₂O₂-hydroquinone induced vitiligo mouse model, through protecting melanocytes from oxidative damage and increasing both exogenous and endogenous melanin content. This study provides valuable insights into vitiligo treatment based on bimetallic organic frameworks.