Amphiphilic-DNA Platform for the Design of Crystalline Frameworks with Programmable Structure and Functionality

Abstract

The reliable preparation of functional, ordered, nanostructured frameworks would be a game changer for many emerging technologies, from energy storage to nanomedicine. Underpinned by the excellent molecular recognition of nucleic acids, along with their facile synthesis and breadth of available functionalizations, DNA Nanotechnology is widely acknowledged as a prime route for the rational design of nanostructured materials. Yet, the preparation of crystalline DNA frameworks with programmable structure and functionality remains a challenge. Here we demonstrate the potential of simple amphiphilic DNA motifs, dubbed C-stars, as a versatile platform for the design of programmable DNA crystals. In contrast to all-DNA materials, in which structure depends on the precise molecular details of individual building blocks, the self-assembly of C-stars is controlled uniquely by their topology and symmetry. Exploiting this robust self-assembly principle we design a range of topologically identical, but structurally and chemically distinct C-stars that following a one-pot reaction selfassemble into highly porous, functional, crystalline frameworks. Simple design variations allow us to fine-tune the lattice parameter and thus control the partitioning of macromolecules within the frameworks, embed responsive motifs that can induce isothermal disassembly, and include chemical moieties to capture target proteins specifically and reversibly.

Cations Regulate Membrane Attachment and Functionality of DNA Nanostructures

“… 26 − 29 Accounting for the effect of (physiological) ions is therefore critical to inform the design of both NA–lipid formulations and membrane-active DNA nanodevices. The latter, in particular, often feature complex and programmable morphologies, charge distributions, and chemical modifications, 9 , 13 , 30 whose coupling with the electrostatic effects mediated by cations could unlock novel functionalities.…”

The effective transfection of a low dose of negatively charged drug-loaded DNA-nanocarriers into cancer cells via scavenger receptors

“…As DNA triangular tiles contain sticky ends, they self-assemble in a robust way to make DNA 2D lattices in the form of sheets that coiled on its (own) axis to form DNA-NWs to act as a drug delivery carrier. FITC-tagged CPT was loaded onto the DNA-NWs using CPT’s binding capability to double-stranded DNA [ 15 ].…”

“…As cancer cells have high proportions of polyanionic ligand-binding scavenger receptors, targeting cancer cells is more effective [ 14 ]. Triangular DNA tiles are synthesized after circularizing the template strand and annealing with staple strands [ 15 , 16 ]. Each triangle tile is designed to contain sticky ends at the vertices to combine (with each other), making a compact polymer, resulting in DNA-nanosheets that fold and spin onto itself due to the helical structure and curvature of the DNA to yield compact DNA-NWs [ 17 , 18 ].…”

Development and functionalization of DNA nanostructures for biomedical applications

“…The DNA tile was synthesized by knotting linear strands into branched arrays as the highly flexible components 16 . The limited linear and lateral growth of the lattices failed to be configured into regular mono‐crystalline networks 17 . However, double crossover (DX) tiles consisting of two DNA duplexes with swap chains created at two distinct points, resulted in stiffness values that were twice as high as linear DNA (Figure 1).…”