A Synergistic DNA-polydopamine-MnO2 Nanocomplex for Near-Infrared-Light-Powered DNAzyme-Mediated Gene Therapy

DNAzyme is emerging for gene therapy. The administration of the in vivo catalytic activity of DNAzyme has proven important but challenging for clinical applications. Herein, we report a synergistic DNA-polydopamine-MnO2 nanocomplex, which enables near-infrared (NIR)-light-powered catalytic activity of DNAzyme in vivo. The nanocomplex has a hierarchical structure: a DNA nanoframework as the scaffold and polydopamine-MnO2 (PM) as the coating layer. The DNA nanoframework contains repeated DNAzyme sequences. PM assembles on the surface of the DNA nanoframework. When the nanocomplex accumulates at tumor sites, upon NIR-light radiation, polydopamine induces a temperature elevation at tumor sites via photothermal conversion; meanwhile, glutathione triggers decomposition of PM to release Mn2+ to activate DNAzyme in the cytoplasm for gene regulation. In vitro and in vivo experiments show that the PM-induced temperature elevation enhances the Egr-1 mRNA cleavage activity of DNAzyme, promoting downregulation of the Egr-1 protein in tumor cells. In addition, the temperature elevation induces heat stress, achieving a synergistic tumor ablation effect.

Automated summary

A DNA-polydopamine-MnO2 nanocomplex was developed for near-infrared light-powered catalytic activity of DNAzyme in vivo. The complex can enhance Egr-1 mRNA cleavage activity of DNAzyme, leading to downregulation of Egr-1 protein in tumor cells and achieving a synergistic tumor ablation effect through heat stress induction.