A Hybrid Carrier System Based On Origami Nanostrucutures And Layer-By-Layer Microparticles

Recent progress in DNA nanotechnology allows the fabrication of 3D structures that can be loaded with a large variety of molecular cargos and even be responsive to external stimuli. This makes the use of DNA nanostructures a promising approach for applications in nanomedicine and drug delivery. However, their low stability in the extra- and intracellular environment as well as low cellular uptake rates and release rates from endosomes into the cytoplasm hamper the efficient and targeted use of DNA nanostructures in medical applications. Here, such major obstacles are overcome by integrating DNA origami nanostructures into superordinated layer-by-layer based microparticles made from biopolymers. The modular assembly of the polymer layer allows a high-density incorporation of the DNA structures at different depth. This enables controllable protection of the DNA nanostructures over extended durations in a broad range of extra- and intracellular conditions without compromising the cell viability. Furthermore, by producing protein-complexed DNA nanostructures it is demonstrated that molecular cargo can be conveniently integrated into the developed hybrid system. This work provides the basis for a new multistage carrier system allowing for an efficient and protected transport of active agents inside responsive DNA nanostructures.