Designing Nuclease-Resistant Enzyme-Mimicking Assemblies of Oligonucleotides Through Supramolecular Conjugation with...

The utility of oligonucleotides has evolved beyond merely delivering genetic information to playing a transformative role in functional nanotechnology. Specifically, the enzyme-like properties of catalytic oligonucleotides, including ribozyme, DNAzyme, and their mimics, offer unique opportunities in bioengineering. A primary challenge in leveraging these catalytic oligonucleotide structures in biomedical applications is their susceptibility to degradation by nucleases. Herein, we introduce a high-affinity (10⁷ M^-1) salt-bridge interaction-mediated generalized noncovalent fabrication strategy to construct arrays of oligonucleotide-templated metal complexes, producing catalytically active hierarchical assemblies displaying resistance to nucleases in human serum. The one-dimensional isodesmic polymeric growth of the supramolecular structures between oligonucleotides and guanidinium containing Pt(II)-complex generates Pt···Pt interactions imparting luminescence enhancement (8-10 fold) with long-lived (∼30 ns) excited states. Consequently, light-mediated singlet oxygen generation enables efficient catalytic oxidation of substrates. Notably, the catalytic activity exclusively resembles oxidases, which function in the absence of H₂O₂ (an essential component of peroxidases), unlike conventional nucleotide-based enzyme mimics. The assembly showcases light-dependent anticancer activity in vitro, with excellent biocompatibility. Overall, the ease of production and robustness of functional oligonucleotide-based higher-order materials, coupled with on-demand photoactivation of exclusive oxidase enzyme-like activity, makes the new supramolecular platform a promising candidate for practical biomedical applications.