Directed Assembly of Nucleic Acid-Based Polymeric Nanoparticles from Molecular Tetravalent Cores

Complementary tetrahedral small molecule-DNA hybrid (SMDH) building blocks have been combined to form nucleic acid-based polymeric nanoparticles without the need for an underlying template or scaffold. The sizes of these particles can be tailored in a facile fashion by adjusting assembly conditions such as SMDH concentration, assembly time, and NaCl concentration. Notably, these novel particles can be stabilized and transformed into functionalized spherical nucleic acid (SNA) structures through the incorporation of capping DNA strands conjugated with functional groups. These results demonstrate a systematic, efficient strategy for the construction and surface functionalization of well-defined, size-tunable nucleic acid particles from readily accessible molecular building blocks. Furthermore, because these nucleic acid-based polymeric nanoparticles exhibited enhanced cellular internalization and resistance to DNase I compared to free synthetic nucleic acids, they should have a plethora of applications in diagnostics and therapeutics.