Engineering a Mechanoresponsive DNA Origami Capsule for Drug Delivery to Narrowed Arteries.

Abstract

Since their inception, DNA origami nanostructures (DONs) have attracted great interest for their programmable geometry, nanoscale precision, and biocompatibility. Here, we present mechanoresponsive DONs designed for targeted drug delivery to narrowed or obstructed arteries. Unlike conventional systems triggered by biochemical cues or external stimuli, our capsules respond autonomously to elevated local shear forces characteristic of stenotic blood flow. The design consists of a hollow boxlike structure sealed by two lids connected through flexible DNA springs, enabling mechanical opening under pathological flow conditions. The nanostructures were assembled and characterized by atomic force microscopy and cryo-transmission electron microscopy, and the mechanical response of the DNA springs was evaluated using optical tweezers. The results confirm that the capsules can operate within physiologically relevant force ranges, demonstrating their potential for noninvasive, site-specific drug release. This mechanoresponsive strategy offers a new paradigm for smart, force-activated nanocarriers for targeted diagnosis and therapy.