Active Self-Assembly of Ladder-Shaped DNA Carrier for Drug Delivery

Abstract

With the advent of nanotechnology, DNA molecules have been transformed from solely genetic information carriers to multifunctional materials, showing a tremendous potential for drug delivery and disease diagnosis. In drug delivery systems, DNA is used as a building material to construct drug carriers through a variety of DNA self-assembly methods, which can integrate multiple functions to complete in vivo and in situ tasks. In this study, ladder-shaped drug carriers are developed for drug delivery on the basis of a DNA nanoladder. We first demonstrate the overall structure of the nanoladder, in which a nick is added into each rung of the nanoladder to endow the nanoladder with the ability to incorporate a drug loading site. The structure is designed to counteract the decrement of stability caused by the nick and investigated in different conditions to gain insight into the properties of the nicked DNA nanoladders. As a proof of concept, we fix the biotin in every other nick as a loading site and assemble the protein (streptavidin) on the loading site to demonstrate the feasibility of the drug-carrying function. The protein can be fixed stably and can be extended to different biological and chemical drugs by altering the drug loading site. We believe this design approach will be a novel addition to the toolbox of DNA nanotechnology, and it will be useful for versatile applications such as in bioimaging, biosensing, and targeted therapy.