Structural DNA Nanotechnology-Based Branch-Sprouted Biomimetic Nanobamboo for Efficient Isolation of Rare Circulating...

Because of very few sequence-identified viral scaffolds suitable for origami assembly and the unavailability of tile-based, nondeformable, superlarge DNA structures with architecturally defined collective properties, the biomedical application of structural DNA nanotechnology is hampered. In the current contribution, we demonstrate a backbone-inserted, center-rigidified, stringing-based assembly (CRSA) technology for constructing DNA biomimetic nanobamboo (Apt-BNB) of high aspect ratio, rich with membrane receptor-binding branches. The Apt-BNB structure is additionally rigidified by installing a Y-shaped backbone into the transverse partition and is surrounded by highly oriented tumor cell-binding aptamers. While the DNA nanobamboo has a length of up to 1956.2 nm and a height of 95.0 nm, no curvature and or structural collapse occurs, contributing to a 33-fold enhancement in structural rigidity. The assembly efficiency is up to 90%, and the ability to protect the surface-confined aptamers against enzymatic degradation is enhanced by about 30 times. The as-assembled aptamer-functionalized DNA nanobamboo is demonstrated to be amenable to the isolation of circulating tumor cells (CTCs) from whole blood samples, with a 68.2-fold enhancement in efficiency, implying its potential as a tool to help prevent tumor relapse and metastasis and offering valuable insights into the construction of nondeformable three-dimensional DNA nanostructures for clinical translation in precision medicine.