Nuclease-resistant photo-responsive synthetic “double-stranded DNAzyme”

Abstract

DNA nanotechnology has significantly progressed from basic structural designs to advanced practical applications. The inherent ability of DNA to assemble with small molecules has elevated it to the forefront of biological applications such as biosensing, bioimaging, altering cell behaviour, and therapeutic delivery. Deoxyribozymes (DNAzymes) represent catalytically active DNA molecules, which are essential yet uncommon, making the fabrication of synthetic DNAzymes significant. However, a key challenge in employing DNAzyme nanostructures in biological settings is their susceptibility to degradation by nucleases in the biological milieu. Herein, we introduced a hierarchical assembly of DNA and guanidium containing Pt(II)-complex (Pt G) through supramolecular interactions that display significant resistance to nucleases in human serum. The one-dimensional growth of the supramolecular structures leads to metal-metal bonds that impart luminescence properties with long-lived excited states. Light-mediated singlet oxygen generated from the Pt G·DNA system allows the oxidation of substrates similar to oxidase enzymes. Besides a fundamental understanding of the new hierarchical assembly, the study presents important functional aspects, including the nuclease resistance, robustness, specific oxidase-like function and on-demand light stimulus-dependent activity for practical applications.