Nucleic Acids Based Polyelectrolyte Complexes: Their Complexation Mechanism, Morphology, and Stability

Abstract

Nucleic acids are a special class of negatively charged polymers, and they can complex with cationic small molecules and polymers to form polyelectrolyte complexes of rich morphology. The initial application focuses on gene delivery and typically involves the complexation of DNA with cationic surfactants and homopolymers.Recent research progress has extended to the complexation of nucleic acids with cationic block copolymers and ionic liquids, leading to the observation of unique morphology and stability characteristics and opening up opportunities for new application development. In this perspective article, we review the current understanding on the complexation behavior of nucleic acids with cationic species. We begin by discussing the phase behavior of DNA complexation with cationic surfactants and homopolymers. We then cover the more recent topic of nucleic acids interaction with cationic block copolymers and present the morphology and stability of complex micelles formed using both amphiphilic and hydrophilic block catiomers. Lastly, we examine DNA binding to ionic liquids and introduce new material applications involving ionic liquid stabilized DNA. We conclude the perspective by discussing a number of remaining challenges and future research topics in this exciting field.

Protection of Double-Stranded RNA via Complexation with Double Hydrophilic Block Copolymers: Influence of Neutral Block Length in Biologically Relevant Environments

“…Note that no R H was determined at N/P ratio = 1 for Q 110 polyplexes as large precipitated aggregates/clusters, visible to the naked eye, formed upon mixing at this particular N/P ratio. Instability of polyplexes made of two oppositely charged homopolymers around the isoelectric point is commonly reported in the literature, 50 and our experiments further demonstrate the importance of incorporating a neutral block to sterically stabilize the polyplexes when close to charge neutrality. At higher N/P ratios, the polyplexes obtained with the homopolymer appeared to be stable, likely as a result of higher polyplex charge resulting from the imbalance of the overall number of charges between the polymer and the dsRNA, in agreement with previous literature.…”

Impact of Degree of Ionization and PEGylation on the Stability of Nanoparticles of Chitosan Derivatives at Physiological Conditions

“…The polycation–siRNA interaction and the coacervation process to form nanoparticles is mainly driven by electrostatic attraction between the negatively charged siRNA molecules and the polycations [ 36 ]. The siRNA loading is very dependent of charge ratios (N/P ratio) in the nanoparticle core, i.e., if there are not enough positively charged amines to neutralize the phosphate groups of the nucleic acid, not all of the siRNA will be efficiently loaded by the vector and the resulting complex will have a negative charge [ 5 , 37 ]. Hence, an electrophoretic mobility study can be used to detect compositions (charge ratios) at which the siRNA is not efficiently complexed, which would result in formulations with low therapeutic potential [ 38 ].…”

Sequence Does Not Matter: The Biomedical Applications of DNA-Based Coatings and Cores

“…Further development of DNA drug containers may benefit from the technology of DNA amphiphiles as well as researches primarily aimed at gene therapy such as DNA compaction with polycations [ 37 , 38 ]. DNA amphiphile is a hydrophilic DNA containing a covalently connected hydrophobic moiety, which allows formation of DNA-based micelles and other complex structures.…”