2021

Seitz, Iris; Shaukat, Ahmed; Nurmi, Kurt; Ijäs, Heini; Hirvonen, Jouni; Santos, Hélder A.; Kostiainen, Mauri A.; Linko, Veikko

Nanostructures based on DNA self-assembly present an innovative way to address the increasing needs for target-specific delivery of therapeutic molecules. Currently, most of the chemotherapeutics being used in clinical practice have undesired and exceedingly high off-target toxicity. This is a challenge in particular for small molecules, and hence, developing robust and effective methods to lower these side effects and enhance the antitumor activity is of paramount importance. Prospectively, these issues could be tackled with the help of DNA nanotechnology, which provides a route for fabrication of custom, biocompatible, and multimodal structures, which can, to some extent, resist nuclease degradation and survive in cellular environment. Similar to widely employed liposomal products, the DNA nanostructures (DNs) are loaded with selected drugs, and then by employing a specific stimulus, the payload can be released at its target region. In this review, we explore several strategies and triggers to achieve targeted delivery of DNs. Notably, we explain different modalities through which DNs can interact with their respective targets as well as how structural changes triggered by external stimuli can be used to achieve the display or release of the cargo. Furthermore, we highlight the prospects and challenges of this technology.