(386a) Stimulus-Responsive DNA Nanostructures for Delivery Applications

The ability of DNA to form predictable nanostructures through sequence-directed hybridization has allowed the design of complex supramolecular materials.  Such nanomaterials can organize functional proteins and bioactive molecules in well-designed patterns and are therefore of great interest to biosensing and the delivery of therapeutics.  

To date, mechanical actuation or switching of DNA nanostructures has been largely achieved through the addition of thermodynamically more favorable DNA partners and resulting rearrangement of DNA strands.  However, such approaches require the addition of new DNA strands and generate waste DNA with each cycle, neither of which are suitable for therapeutic delivery strategies.

Here we will show that non-canonical Watson–Crick base pairing provides an in situ approach for actuation through sensitivity to solution conditions. We demonstrate this concept with DNA pyramids containing i-motifs along one face.  By controlling the balance of hydrogen-bonding interactions, these i-motifs can regulate DNA pyramid assembly/disassembly.  The assembly and disassembly are verified by several techniques including electrophoresis, fluorescence, and circular dichroism.  As a proof-of-concept we further show that this disassembly can be used to trigger the release of protein cargo from the DNA pyramids.  Importantly, the pyramid disassembly is triggered with physiologically-relevant acidification, an attractive feature for drug and gene delivery vehicles.