Functionalizing DNA nanostructures with natural cationic amino acids

Abstract

Complexing self-assembled DNA nanostructures with various functional guest species is the key to unlocking new and exciting biomedical applications. Cationic guest species not only induce magnesium-free DNA to self-assemble into defined structures but also endow the final complex nanomaterials with new properties. Herein, we propose a novel strategy that employs naturally occurring cationic amino acids to induce DNA self-assembly into defined nanostructures. Natural l -arginine and l -lysine can readily induce the assembly of tile-based DNA nanotubes and DNA origami sheets in a magnesium-free manner. The self-assembly processes are demonstrated to be pH- and concentration-dependent and are achieved at constant temperatures. Moreover, the assembled DNA/amino acid complex nanomaterials are stable at a physiological temperature of 37 °C. Substituting l -arginine with its D form enhances its serum stability. Further preliminary examination of this complex nanomaterial platform for biomedical applications indicates that DNA/amino acids exhibit distinct cellular uptake behaviors compared with their magnesium-assembled counterparts. The nanomaterial mainly clusters around the cell membrane and might be utilized to manipulate molecular events on the membrane. Our study suggests that the properties of DNA nanostructures can be tuned by complexing them with customized guest molecules for a designed application. The strategy proposed herein might be promising to advance the biomedical applications of DNA nanostructures.

An mTOR siRNA‐Loaded Spermidine/DNA Tetrahedron Nanoplatform with a Synergistic Anti‐Inflammatory Effect on Acute Lung Injury

“…Noncanonical self-assembly of DNA with guest molecules is a promising strategy to construct DNA nanostructures with new properties and subsequently extend their biomedical applications. For example, endogenous polyamines, [12] carbon quantum dots, [13] and amino acids [14] are capable of assembling DNA in a magnesium-free manner. Spermidine, a natural polyamine, has three positive charges and can interact with nucleic acids and proteins.…”

Materialistic Interfaces with Nucleic Acids: Principles and Their Impact

“…Positive molecules and proteins [35] Molecular assembly Stimuli-responsive biosystem, bio-imaging Positively charged nanomaterials (gold nanoparticles, [172] and luminescent nanodots et al) [107] Photothermal and photodynamic effects, fluorescence properties Gene regulation, immunoassay, immunotherapies, advanced chemical therapy Lipids, [81] lipidoids, polymers [97] High uptake efficacy, endosomal escape, membrane fusion Chemical therapies, gene therapies, immunotherapies…”

“…It was demonstrated that cationic guest species not only resulted in the formation of DNA nanoarchitectures with defined structures but also induced the complex nanomaterials with emerging biological characteristics. [ 35 ] Similarly, spermidine could adjust the isothermal self‐assembly of DNA nanoprisms. In comparison to conventional Mg 2+ ‐assembled DNA nanoprisms, the spermidine‐DNA nanoprisms show higher thermal ability and enhanced resistance to enzymatic degradation.…”

“…It was reported that cationic amino acids such as lysine and arginine are capable of assembling both tile‐based and origami DNA nanostructures in a solution without the magnesium ions. [ 35 ] Simmel and coworkers showed that endogenous polyamines can facilitate DNA origami self‐assembly without any metallic cation involved. They further demonstrated the potential of DNA origami for drug delivery using electrotranfection technique.…”

Protein-mediated DNA self-assembly by controlling the surface charge in a molecular crowding environment

“…Previously, we showed that cationic amino acids such as arginine and lysine are capable of facilitating DNA self-assembly into defined nanostructures. 26 In another study, Markvoort et al revealed the counterion-dependent stabilization mechanisms by atomistic molecular simulation. 27 Oligolysines stabilize DNA by connecting adjacent DNA helices and preventing helix repulsion simultaneously.…”