Layer-by-Layer modified DNA Origami Nanostructures as a Smart Tool for Drug Delivery

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DNA origami nanostructures, three-dimensional formations made of long single-stranded scaffold DNA and short connecting staple oligonucleotides, possess a high versatility in application as smart drug delivery systems (sDDS) in cells. Compared to other DDS, they can be conveniently equipped with “programmable” lids by adding lock elements to the structure, which can be opened by a specific key. However, for biomedical applications several drawbacks still remain: A controllable application to the desired cells and the accessibility of the cytoplasm are severely limited due to low uptake and limited equipment with specific functional components. Particularly, stability is very restricted in protease- and enzyme-rich environments as well as low salt concentrations; conditions usually found in blood serum and endolysosomal cell compartments.In this project our emphasis is on those drawbacks by investigating layer-by-layer (LbL) based polymer coating on origami in different approaches: 1) Micrometer-sized hybrid carriers (3-5µm) will be designed by integrating origami nanostructures (switchability, controlled burst release) in a LbL multilayer (protection, controlled origami release, independent assembly of functional components/key elements) assembled on a spherical template. Combining the advantages of both carrier types, origami properties can be investigated in a defined way as well as a multifunctional carrier for drug delivery is already available. 2) This hybrid carrier will be down-sized (100-500nm) to enhance the transport properties in blood. 3) The LbL technique will be transferred onto the origami nanostructure (40-120nm) itself by adapting the biopolymer coating conditions.Within all three approaches, the emphasis is on the preservation of the lock opening as well as the addition of functional components to the multilayer. In this context, design, desired effect and efficiency will be studied under model and cellular conditions as well as by application of model and specific (siRNA) agents. Those investigations will strongly enhance the options of defined delivery.