DNA nanotechnology—the research field using DNA molecules as building material—has developed rapidly during recent years and enabled the construction of increasingly complex nanostructures. DNA nanostructures, such as DNA origami, serve as an excellent foundation for nanocarrier-based drug delivery applications, and examples of their use in medical treatments have already been demonstrated. Although the stability of such DNA nanostructures under physiological conditions can be improved, little is known about their digestion by endonucleases, which, found everywhere in our blood and tissues, are responsible for destroying foreign DNA in our bodies.