DNA–Polyelectrolyte Complexation Study: The Effect of Polyion Charge Density and Chemical Nature of the Counterions

Abstract

Complexes of polycations and DNA, also known as polyplexes, have been extensively studied in the past decade, as potential gene delivery systems. Their stability depends strongly on the characteristics of the polycations, as well as the nature of the added salt. We present here a study of the DNA ionene complexation in which we used fluorescence, UV, and CD spectroscopy, combined with molecular dynamics computer simuations, to systematically examine the influence of the polycation charge density, as well as the influence of the nature of the counterion, on the stability of these systems. Ionenes as polycations, depending on their structural characteristics, have previously been found to possess low cytotoxicity, and are therefore particularly interesting as potential gene delivery agents. The results show that the DNA solutions in the presence of the polycation are more stable in the case of very large or very small ionene charge density, suggesting different mechanism of complexation. The computer simulations show that the ionenes with high charge density bind to the minor groove of the DNA molecules, while the ionenes with lower charge density bind to the major groove of the DNA. The nature of the counterions play only a minor role: precipitation of the DNA molecules occurs at slightly lower ionene concentration when fluoride counterion are present, compared to the bromide counterions.

Critical Assessment of the Interaction between DNA and Choline Amino Acid Ionic Liquids: Evidences of Multimodal Binding and Stability Enhancement

“…The MD simulation of the DNA-CAAIL ligand system in aqueous medium was performed to investigate the structural dynamics of the DNA−ligand interaction, as well as the relative population of various modes of binding of the ligand. Mojca et al 63 in their recent article showed the influence of charge density of ionene in the stability of DNA and found negligible effect of ionene anion on DNA binding by combined study of experimental and theoretical calculation. Chandran et al 9 through spectroscopic and MD simulation results suggest that electrostatic, hydrophobic, and polar interactions of IL cations play significant role in DNA stability.…”

In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA

“…Important insight on the interactions of nucleic acids with polycationic polymers can already be obtained by using simple model systems of rather limited sizes compared to corresponding experimental systems (27,28,53,54). However, considering that the focus on this study is on the effect of the relative amount of the "stealth" agent vs the polycation on the binding to DNA, and that charge polymers "end effects" are known to affect the electrostatic interactions, we did limit the gap between the computational and experimental systems, by using vector and DNA molecule of the same size in the "in vitro" and "in silico" experiments.…”

Recent Advances in Hybrid Biomimetic Polymer-Based Films: from Assembly to Applications

“…The stability of polyplex films based on DNA depends strongly on the characteristics of the polycations, as well as the nature of the added salt [149,150]. Binding interactions between DNA and cationic nanocarriers must be sufficiently strong to prevent nuclease-mediated degradation, yet weak enough to permit transcription [42].…”