Hierarchical Assembly of Multilayer Core–Shell DNA Origami Crystals

ABSTRACT A multilayer core–shell architecture capable of selectively capturing distinct nanomaterials into a predetermined layer is anticipated to facilitate multifunctional isolation or cascade processes at the microscale. However, fabricating single‐crystal architectures featuring numerous shells with intricate distribution patterns remains challenging. In this study, we employed DNA nanotechnology to construct microscale multilayer core–shell DNA origami crystals. The internal layers exhibit tunable properties, including size, quantity, self‐similarity, and morphology. The shell size can be regulated from 700 to 1800 µm 3 , and the layer quantity can be extended to five. We also fabricated eight distinct crystals exhibiting non‐self‐similarity and two types of heteromorphic core–shell crystals. Each layer has operational independence, allowing the customized capture of nanomaterials and implementation of compartmentalized reactions. These multilayer core–shell crystals have potential for serving as compartmentalization templates for functional units, which may provide possibilities for simulating cell work or constructing artificial organelles.