G-Quadruplex-Mediated Molecular Switching of Self-Assembled 3D DNA Nanocages

We have demonstrated a strategy to reversibly extend and contract 3D DNA nanocages based on stimuli-responsive G-rich DNA strand as a scaffold. The contraction and extension of nanocage would be regulated by formation and deformation of G-quadruplex in the presence of K+ ions and chelating agents respectively. As opposed to a single human telomeric strands (HTL), the advantage of integrating three HTLs into 3D DNA structure for molecular switching is that multi G-rich oligonucleotide sequences which extensively exist in living environments and play important roles in biological mechanisms, can be simultaneously introduced to the self-assembled DNA system with versatile functionalities while conformational changes can be rationally designed and controlled by different stimuli/targets. In addition, compared to single telomeric DNA strands, self-assembled 3D DNA nanocages act as horseradish peroxidase mimicking DNAzymes for colorimetric detection and monitoring of cholesterol with high stability toward nuclease and blood serum degradations. Overall, this is the first example of facile construction of 3D DNA nanostructures with contractile, reversible, and catalytic features based on the assembly and disassembly of G-quadruplexes. This work offers a new platform for manipulation of nanoscale conformational changes and a step forward in obtaining stimuli-responsive 3D DNA nanomaterials with versatile reactivity and functionalities.