“Giant Surfactants” Created by the Fast and Efficient Functionalization of a DNA Tetrahedron with a Temperature-Responsive Polymer

Abstract

Copper catalyzed azide-alkyne cycloaddition (CuAAC) was employed to synthesize DNA block copolymers (DBCs) with a range of polymer blocks including temperature-responsive poly(N-isoproylacrylamide) (poly(NIPAM)) and highly hydrophobic poly(styrene). Exceptionally high yields were achieved at low DNA concentrations, in organic solvents, and in the absence of any solid support. The DNA segment of the DBC remained capable of sequence-specific hybridization: it was used to assemble a precisely defined nanostructure, a DNA tetrahedron, with pendant poly(NIPAM) segments. In the presence of an excess of poly(NIPAM) homopolymer, the tetrahedron-poly(NIPAM) conjugate nucleated the formation of large, well-defined nanoparticles at 40 °C, a temperature at which the homopolymer precipitated from solution. These composite nanoparticles were observed by dynamic light scattering and cryoTEM, and their hybrid nature was confirmed by AFM imaging. As a result of the large effective surface area of the tetrahedron, only very low concentrations of the conjugate were required in order for this surfactant-like behavior to be observed.

Bio-surface engineering with DNA scaffolds for theranostic applications

“…Liu et al [67] introduced a hydrophobic DNA-surfactant complex in an organic phase for nucleic acid modification and polymerization, producing various amphiphile-DNA nanostructures and DNA side chain polymers. Andreas Herrmann group exploited a DNA tetrahedron with pendant poly (N-isoproylacrylamide) segments for assembling a precisely defined composite nanoparticles [68].…”

Photocontrolled micellar aggregation of amphiphilic DNA-azobenzene conjugates

“…To react an oligonucleotide with hydrophobic molecules, which typically involves organic solvents, optimization of the reaction conditions is required, including the choice of catalyst, solvent combination, and ligand-to-copper catalyst ratios, to achieve reliable and efficient reactions [15,41]. However, copper is cytotoxic, and even residual trace amounts of copper remaining in the reaction products may severely limit the practical use of Click chemistry in a biological context [42].…”

“…To increase the resolution in the MALDI mass measurements, a shorter oligonucleotide (Cy3-T 15 Moreover, the MALDI mass spectrum of the functionalized oligonucleotides only shows one high molecular weight peak, which suggests that all Cy3-T 15 -N 3 were converted to Cy3-T 15 -azobenzene amphiphiles, and thus indicates a high efficiency of our copperfree Click reaction. As shown in Fig.…”

“…Finally, temperatureresponsive DNA-poly(N-isopropylacrylamide) micelles were demonstrated by Wilks et al. [15].…”

Efficient DNA–Polymer Coupling in Organic Solvents: A Survey of Amide Coupling, Thiol-Ene and Tetrazine–Norbornene Chemistries Applied to Conjugation of Poly(N-Isopropylacrylamide)

“…They used DNA to control the precise placement of polymer domains within hybrid structures, and demonstrated the ability of polymers conjugated to DNA to form discrete nanocube structures, which predictably changed the polymer’s self-assembly behaviour, as well as introducing a new driving force for the assembly of DNA nanostructures in the form of hydrophobic interactions13141516. Our own group also made the first report of a DNA-polymer conjugate in which the DNA was used to form part of a discrete nanostructure, in this case a DNA tetrahedron17. The polymer used here was temperature-responsive, leading to the formation of dynamic higher order DNA–polymer structures in solution.…”