Spatial control over the distribution of therapeutics is a highly desired feature, which could limit the side effects of many drugs. Here we describe a nanoscale agent, fabricated from a coupled polymer-DNA origami hybrid that exhibits stability in serum and slow diffusion through tissues, in a manner correlating with shape and aspect ratio. Coupling to fragments of polyethylene glycol (PEG) through polyamine electrostatic interactions resulted in marked stability of the agents in-vivo, with > 90% of the agents maintaining structural integrity 5 days following subcutaneous injection. An agent functionalized with aptamers specific for human tumor necrosis factor TNF-alpha, significantly abrogated the inflammatory response in a delayed-type hypersensitivity model in humanized TNF-alpha mice. These findings highlight polymer-DNA hybrid nanostructures as a programmable and pharmacologically viable update to mainstream technologies such as monoclonal antibodies, capable of exerting an additional layer of control across the spatial dimension of drug activity.
© 2023. The Author(s).