Cation-Responsive and Photocleavable Hydrogels from Noncanonical Amphiphilic DNA Nanostructures

Abstract

Thanks to its biocompatibility, versatility, and programmable interactions, DNA has been proposed as a building block for functional, stimuli-responsive frameworks with applications in biosensing, tissue engineering, and drug delivery. Of particular importance for in vivo applications is the possibility of making such nanomaterials responsive to physiological stimuli. Here, we demonstrate how combining noncanonical DNA G-quadruplex (G4) structures with amphiphilic DNA constructs yields nanostructures, which we termed "Quad-Stars", capable of assembling into responsive hydrogel particles via a straightforward, enzyme-free, onepot reaction. The embedded G4 structures allow one to trigger and control the assembly/disassembly in a reversible fashion by adding or removing K + ions. Furthermore, the hydrogel aggregates can be photo-disassembled upon near-UV irradiation in the presence of a porphyrin photosensitizer. The combined reversibility of assembly, responsiveness, and cargo-loading capabilities of the hydrophobic moieties make Quad-Stars a promising candidate for biosensors and responsive drug delivery carriers.

Reaction–Diffusion Patterning of DNA-Based Artificial Cells

“…Our condensates self-assemble from branched amphiphilic DNA nanostructures, as shown in Figure b. Similar constructs were previously demonstrated to form nanoporus phases with programmable structures, molecular-sieving properties, stimuli responsiveness, and the ability to host dynamic DNA circuitry. − As depicted in Figures c and S1 and detailed in the Experimental Methods (SI), spherical aggregates with cell-like dimensions (10–40 μm in diameter) readily emerge from a one-pot annealing reaction. Small-angle X-ray scattering measurements demonstrate that the condensates display internal crystalline order with a BCC unit cell and lattice parameter of 26.8 nm, which is consistent with previous observations on similar systems (Figure S2).…”

Advances and prospects of dynamic DNA nanostructures in biomedical applications

“…Secondly, they rely on ion-stimulated molecules, which mainly refer to G-quadruplex. In the absence of particular metal ions such as K + , 24 Mg 2+ , Pb 2+ , 25 Hg 2+ , Ag + , Cu 2+ , Ca 2+ , Sr 2+ , etc., G-rich ssDNA undergoes conformational change to form stabilized G-quadruplex. 26 Generally, those DNA nanostructures mediated by metal ions can be used to detect the presence of specic metal ions, which become potential intelligent materials in the applications in the eld of environmental and food safety monitoring.…”

“…Secondly, they rely on ion-stimulated molecules, which mainly refer to G-quadruplex. In the absence of particular metal ions such as K + , 24 Mg 2+ , Pb 2+ , 25 Hg 2+ , Ag + , Cu 2+ , Ca 2+ , Sr 2+ , etc. , G-rich ssDNA undergoes conformational change to form stabilized G-quadruplex.…”

Reaction-diffusion patterning of DNA-based artificial cells

“…Similar constructs were previously demonstrated to form nanoporus phases with programmable structure, molecular-sieving properties, stimuli responsiveness, and the ability to host dynamic DNA circuitry. 23–25,28,29 As depicted in Fig. 1B, Figure S1 (SI), and detailed in the Experimental Methods (SI), spherical aggregates with cell-like dimensions (10 - 40 μm in diameter) readily emerge from a one-pot annealing reaction.…”