Abstract
A DNA tetrahedron as the most classical and simplest three-dimensional DNA nanostructure has been widely utilized in biomedicine and biosensing. However, the existing assembly approaches usually require harsh thermal annealing conditions, involve the formation of unwanted by-products, and have poor size control. Herein, a facile strategy to fabricate a discrete DNA tetrahedron as a single, thermodynamically stable product in a quantitative yield at room temperature is reported. This system does not require a DNA trigger or thermal annealing treatment to initiate self-assembly. This DNA tetrahedron was made of three chemically ligated triangular-shaped DNAs in unconventional ladder-like arrangements, with measured heights of ∼4.16 ± 0.04 nm, showing extra protections for enzymatic degradation in biological environment. They show substantial cellular uptake in different cell lines via temperature, energy-dependent and clathrin-mediated endocytosis pathways. These characteristics allow our DNA tetrahedron to be used as vehicles for the delivery of very small and temperature-sensitive cargos. This novel assembly strategy developed for DNA tetrahedra could potentially be extended to other highly complex polyhedra; this indicated its generalizability.
Highlights
With the rapid development of DNA nanotechnology, various bottom-up self-assembly strategies have been utilized to construct DNA nanostructures with different shapes and sizes.[1,2] These nanostructures have been used for in vitro applications such as nanotools for molecular biology, biosensors, and smart nanodevices.[3,4,5] Due to their excellent biocompatibility and cellular permeability, they have become a promising platform for drug delivery applications.[6,7] As the most classical and simplest three-dimensional (3D) structure, a DNA tetrahedron can be synthesized by mixing four singlestranded DNAs in one-pot a er a quick thermal annealing process.[8]
A erwards, native polyacrylamide gel electrophoresis (PAGE) analysis con rmed the stepwise addition of the three pairs DNA building blocks (P1 to P3) to form a discrete pyramidal DNA tetrahedron at room temperature within 10 min (Scheme 1 and Fig. 1c)
An extended half-life of 3.95 h has been obtained when compared with that of the duplex DNA strands that degrade within 15 min.[36]. These results suggested that this newly designed DNA tetrahedron structure consisting of three fully ligated DNA strands could provide extra protections for enzymatic degradation
Summary
With the rapid development of DNA nanotechnology, various bottom-up self-assembly strategies have been utilized to construct DNA nanostructures with different shapes and sizes.[1,2] These nanostructures have been used for in vitro applications such as nanotools for molecular biology, biosensors, and smart nanodevices.[3,4,5] Due to their excellent biocompatibility and cellular permeability, they have become a promising platform for drug delivery applications.[6,7] As the most classical and simplest three-dimensional (3D) structure, a DNA tetrahedron can be synthesized by mixing four singlestranded DNAs in one-pot a er a quick thermal annealing process.[8]. The two open ends of the three CTS strands were hybridized to their corresponding complementary DNA strands L1, L2, and L3 followed by a chemical ligation reaction using cyanogen bromide to generate three closed and cyclic triangular-shaped DNA building blocks (T1, T2 and T3) with yields ranging from 25% to 35%.21 These cyclic products were puri ed and characterized by denaturing PAGE (Fig. 1a) and MALDI-TOF mass spectroscopy analyses (Fig. S1†).
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