Functional DNA–Polymer Conjugates

Abstract

DNA nanotechnology has seen large developments over the last 30 years through the combination of solid phase synthesis and the discovery of DNA nanostructures. Solid phase synthesis has facilitated the availability of short DNA sequences and the expansion of the DNA toolbox to increase the chemical functionalities afforded on DNA, which in turn enabled the conception and synthesis of sophisticated and complex 2D and 3D nanostructures. In parallel, polymer science has developed several polymerization approaches to build di-and triblock copolymers bearing hydrophilic, hydrophobic, and amphiphilic properties. By bringing together these two emerging technologies, complementary properties of both materials have been explored; for example, the synthesis of amphiphilic DNA−polymer conjugates has enabled the production of several nanostructures, such as spherical and rod-like micelles. Through both the DNA and polymer parts, stimuli-responsiveness can be instilled. Nanostructures have consequently been developed with responsive structural changes to physical properties, such as pH and temperature, as well as short DNA through competitive complementary binding. These responsive changes have enabled the application of DNA−polymer conjugates in biomedical applications including drug delivery. This review discusses the progress of DNA−polymer conjugates, exploring the synthetic routes and state-of-the-art applications afforded through the combination of nucleic acids and synthetic polymers.

Combined Therapeutics for Atherosclerosis Treatment Using Polymeric Nanovectors

“…Finally, the release of miRNA from the NPs at pH 7.4 was observed to be larger than that of the drug, with 36 and 67% after 10 and 170 h, respectively. This enhanced release rate compared to ATOR clearly stems from the location of the miRNA onto the NP surfaces; although miRNA is associated through complexation with chitosan, which stabilizes NPs, the Donnan effect and the presence of anionic species in solution help in progressively dissociating such complexes, thus favoring the release of the bioactive compound [47,48]. The observed incomplete cumulative release profiles of both cargoes result from the combination of a relatively limited time interval for release studies and the existence of strong polymer-cargo interactions, hindering the drug release [49,50].…”

Chemically modified DNA nanostructures for drug delivery

“…Various organic reactions have been developed for the chemical modification of DNA. 50 , 51 Based on additional covalent bonds, the chemically modified DNA can facilitate structural assembly and cargo loading. Meanwhile, chemical modification can also protect DNA nanostructures from enzymatic digestion to enhance stability.…”

DNA Sequence and Length Dictate the Assembly of Nucleic Acid Block Copolymers

“…Sequence-defined DNA amphiphiles are covalent polymer chains of monodisperse length and specific monomer order attached to single-stranded DNA, constructed efficiently and rapidly on an automated DNA synthesizer. [1][2][3][4][5][6][7][8][9][10] Self-assembly arises to minimize contact of the hydrophobic region with water, and the relative volume of the hydrophobic to hydrophilic block can play a major role in determining the assembly morphology. [11][12][13] Increasing the volume of the hydrophobic phase generally decreases the interfacial curvature (i.e., the curvature of the hydrophobic region at the interface between the two blocks) evolving the morphology from spheres to cylinders to lamellae.…”

“…14,15 In the case of DNA block copolymers, this yields supramolecular structures with DNA coronas that can be addressed with functional moieties for numerous biological and materials applications. 7,[16][17][18][19][20] Our group 3,9,[21][22][23] and others 24,25 have explored modulation of the hydrophobic moiety -its size, chemistry and number of repeat monomers -in forming diverse structures, but rarely has altering the hydrophilic DNA chain been investigated as a driving force in self-assembly. 26,27 Single-stranded DNA (ssDNA) chains are not always disordered polymers -electrostatics, π interactions, and base hydrophobicity can alter the conformation, rigidity, and internal structure of ssDNA.…”