# DNA Origami‐Templated Aptamer Chiral Structures Realize Cellular Enantioselectivity

## TL;DR

Researchers used DNA origami to create chiral aptamer structures that interact differently with cancer cells, improving drug delivery and cell killing.

## Contribution

Aptamers arranged in left- or right-handed patterns on DNA tubes show enantioselective cellular interactions and drug delivery efficacy.

## Key findings

- Left-handed DNA tube-aptamer structures show higher cell uptake than right-handed ones.
- Left-handed constructs loaded with Daunorubicin show over double the cytotoxicity in cancer cells.
- Chiral patterns influence protein dimerization and internalization of DNA-aptamer complexes.

## Abstract

Chirality refers to handedness as left‐ or right‐handed form of a molecule or molecular construct by synthesis or self‐assembly. In biology, chirality plays critical roles in determining the structures and functions of biomolecules such as proteins. In this study, we demonstrated that structural chirality generated by patterning multiple cell surface protein biomarker‐binding aptamers on a tubular‐shaped DNA origami (“DNA tube”) can realize differentness in cellular interaction, nanostructure uptake, cancer drug delivery, and consequent cell killing. Formation of the DNA tube and its ability to arrange external elements into left‐ or right‐handed form have been characterized by gel electrophoresis, atomic force microscopy, and transmission electron microscopy. Our fluorescence‐based cell experiments showed that the DNA tube‐templated aptamers of a left‐handed pattern can yield a higher cell uptake than those in a right‐form pattern. When loaded with an anticancer drug, Daunorubicin (Dau), the left‐handed tube‐aptamer‐Dau construct showed greater than double the cancer cell cytotoxicity than the construct in the right‐handed. Our study not only revealed that cell surface proteins interaction with the aptamers spatially organized into different chiral patterns can yield different cellular interaction and internalization efficiencies, but offered a new and versatile cancer drug delivery strategy for enhanced target cell treatment efficacy.

Aptamers displayed on tubular DNA origami nanostructures in defined chiral orientations (left‐ or right‐handed) exhibit enantioselective interactions with cell surface target proteins. While the right‐handed configuration supports only transient binding, the left handedness energetically favors protein dimerization and promotes subsequent internalization of the origami‐aptamer‐protein complex. This enantioselective behavior may be leveraged for diverse therapeutic applications, including targeted drug delivery to cancer cells.