Although non-specific entrapment of functional proteins has been successfully demonstrated in all-DNA 3D crystals, site specific positioning has been achieved only in 2D DNA architectures. Owing to their controllable porosity and resilience to changes in building-block design, C-star frameworks offer an attractive platform for site-selective entrapment of functional macromolecules, including proteins, in 3D. Following the strategy applied for 2D nanostructures, to obtain protein-binding capability in 3D frameworks we designed a C-star variant with l = 28, in which one arm was modified to host a nitrilotriacetic acid (NTA) molecule (see Fig. (ii)). When charged with Ni 2+ ions, NTA can specifically bind recombinant proteins featuring poly-histidine residues (His-tags).