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

Abstract

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.

Nanoparticle-Programmed Surface for Drug Release and Cell Regulation via Reversible Hybridization Reaction

“…24–27 Moreover, they can be physically or chemically functionalized with biomolecules such as peptides, antibodies, and nucleic acids. 28–30 Based on the functionalization, nanoparticles can acquire the function of molecular recognition. Notably, while nanoparticles often exhibit unique properties and functions different from bulk materials, they still possess certain key features of bulk materials.…”

The competing effects of core rigidity and linker flexibility in the nanoassembly of trivalent small molecule-DNA hybrids (SMDH3s)–a synergistic experimental-modeling study

“…As a versatile, scalable synthon, synthetic DNA has been tethered to many building blocks such as small organic molecules, dendrimers, polymers, and metallic nanoparticles, which can then form a variety of hybrid nanomaterials 1–5 with many applications in diagnostics 2,6,7 and therapeutics. 5,8 Given the synthetic ease with which the sugar-phosphate backbone can be manipulated and the high sequence-specificity of nucleotide base pairing, DNA-functionalized supramolecular assemblies 9–13 and nanostructures 14–20 have also provided a fertile ground for the exploration of new nanomaterials design principles.…”

“…5,8 Given the synthetic ease with which the sugar-phosphate backbone can be manipulated and the high sequence-specificity of nucleotide base pairing, DNA-functionalized supramolecular assemblies 9–13 and nanostructures 14–20 have also provided a fertile ground for the exploration of new nanomaterials design principles. For this purpose, small molecule-DNA hybrids (SMDHs), where the number, orientation, and length of the DNA arms attached to small organic cores can be precisely tuned via covalent bonds, 5,9,10,21,22 have emerged as a prominent testbed for the elucidation of supramolecular and nanoassembly principles. 9–11,22–25 …”

“…Recent advances in the efficient synthesis of SMDHs possessing a broad range of organic cores, 9,10,12,13,21,22,24–27 spacers, and DNA sequences have greatly increased the scope and versatility of these building blocks in the design and construction of hybrid nanomaterials such as well-defined supramolecules, 9,12,13,28 nucleic acid-based polymeric nanoparticles, 5 and DNA-directed crystal lattices. 29 In spite of these exciting developments, it is still difficult to predict and experimentally control the desirable outcome of SMDH nanoassembly as a systematic function of supramolecular flexibility, oligonucleotide concentration, and DNA arm length.…”

“…However, as core 1 is not representative of the broad ranges of currently known SMDH nanoassemblies, many of which have employed highly rigid aromatic organic cores (e.g., 2 , 3 , and 4 in Fig. 1), 5,9,10,12,13,21,24 a more general model must be developed that can account for the roles that core-centric factors–such as the rigidity and geometry of the organic cores and the connection between the core and the DNA arms–may play in the nanoassemblies of SMDH-based building blocks.…”