Transmembrane capability of DNA origami sheet enhanced by 3D configurational changes

DNA origami-engineered nanostructures are widely used in biomedical applications involving transmembrane delivery. Here, we propose a method to enhance the transmembrane capability of DNA origami sheets by changing their configuration from two-dimensional to three-dimensional. Three DNA nanostructures are designed and constructed, including the two-dimensional rectangular DNA origami sheet, the DNA tube, and the DNA tetrahedron. The latter two are the variants of the DNA origami sheet with three-dimensional morphologies achieved through one-step folding and multi-step parallel folding separately. The design feasibility and structural stability of three DNA nanostructures are confirmed by molecular dynamics simulations. The fluorescence signals of the brain tumor models demonstrate that the tubular and the tetrahedral configurational changes could dramatically increase the penetration efficiency of the original DNA origami sheet by about three and five times, respectively. Our findings provide constructive insights for further rational designs of DNA nanostructures for transmembrane delivery.