The work herein describes a novel of class of hybrid materials consisting of synthetic DNA-polymer amphiphiles that self-assemble into discrete micellar nanoparticles whose physical and chemical properties depend on both the nature of the DNA sequence as well as the chemical composition of the polymer. These materials address three key concerns with respect to chellenges in DNA delivery. 1) They arrange DNA in a dense array at the nanoparticle surface, protecting the nucleic acid shell from nuclease degradation. 2) They undergo rapid cellular uptake, distribute into the cytosol, and hybridize in a sequence-specific fashion to designated mRNA sequences. 3) They are capable of dramatic response to specific nucleic acid and enzymatic stimuli.Current efforts to deliver nucleic acids into key cellular regions depend on methods that necessarily preclude in vivo studies, require unpredictable viral vectors, or rely on ill-defined non-covalent polyplex aggregates that take advantage of membrane disruption and hence tend to be relatively toxic. Recently, spherical nucleic acids have been developed, taking advantage of the three-dimensional arrangement of nucleic acids at gold nanoparticle surfaces to confer unique properties upon the attached nucleic acids. Importantly, these materials have been demonstrated to undergo cellular internalization and furthermore interact specifically with intracellular RNA. The key distinction highlighted in our approach is the ability to couple these specific interactions with material function that is guided not only by the DNA at the nanoparticle surface but also by the sequestered polymer in the core of the material. With such materials in hand, our efforts are focused on the development of systems that utilize biological information to function in a stimuli-responsive fashion in crowded, complex, and hostile biological environments. Probing and tuning these types of interactions will be vital in advancing functional nanomaterials at the biological interface.

Nucleic acid-programmed polymeric nanomaterials for biological communication

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.