Dicationic Surfactants with Glycine Counter Ions for Oligonucleotide Transportation

Abstract

Gemini surfactants are good candidates to bind, protect, and deliver nucleic acids. Herein, the concept of amino acids (namely glycine) as counter ions of gemini surfactants for gene therapy application was explored. This study was conducted on DNA and RNA oligomers and two quaternary bis-imidazolium salts, having 2,5-dioxahexane and 2,8-dioxanonane spacer groups. The toxicity level of surfactants was assessed by an MTT assay, and their ability to bind nucleic acids was tested through electrophoresis. The nucleic acid conformation was established based on circular dichroism and infrared spectroscopic analyses. The structures of the formed complexes were characterized by small-angle scattering of synchrotron radiation. Both studied surfactants appear to be suitable for gene therapy; however, although they vary by only three methylene groups in the spacer, they differ in binding ability and toxicity. The tested oligonucleotides maintained their native conformations upon surfactant addition and the studied lipoplexes formed a variety of structures. In systems based on a 2,5-dioxahexane spacer, a hexagonal phase was observed for DNA-surfactant complexes and a micellar phase was dominant with RNA. For the surfactant with a 2,8-dioxanonane spacer group, the primitive cubic phase prevailed.

Clear distinction between CAC and CMC revealed by high-resolution NMR diffusometry for a series of bis-imidazolium gemini surfactants in aqueous solutions

“…59 Additionally, determination of CAC and CMC values for gemini surfactants is essential for optimization of their usage as delivery systems for nucleic acid in gene therapy. 60,61 They are extremely efficient at condensing DNA and RNA molecules and therefore can be used at low concentrations, what reduces the adverse cytotoxicity effects. Those properties are attributed to low CMC of gemini surfactants.…”

The Process of Binding and Releasing of Genetic Material from Lipoplexes Based on Trimeric Surfactants and Phospholipids

“…Synthetic amphiphilic compounds from a group of dicationic (gemini-type) surfactants or higher oligomeric forms can effectively bind nucleic acids; however, they exhibit higher toxicity to living cells. Moreover, trimeric surfactants studied in this paper are characterized by higher cytotoxicity than dimeric surfactants already described by Pietralik et al [17]. Therefore, combining selected trimeric surfactants with phospholipids can reduce the toxicity of the surfactants, while maintaining good complexity of the genetic material.…”

“…The downside of polymeric surfactants is increased toxic effects. Trimeric surfactants studied in this work are characterized by higher cytotoxicity than dimeric surfactants of similar composition already described in [ 15 , 17 ]. The EC 50 value (the concentration at which 50% of the cells died) for TRI_N surfactant was assessed as 15 ± 3 μM whereas its dimeric analogue was characterized by almost three times higher value (42.2 ± 0.2 μM) [ 15 ].…”

“…In our research to date, we have focused mainly on the use of dicationic surfactants to create stable and nontoxic lipoplexes with nucleic acids, both siRNA oligomers and long and short DNA fragments [ 12 , 15 , 16 ], also including surfactants with amino acids molecules (glycine) as counter ions [ 17 ].…”

Ammonium Gemini Surfactants Form Complexes with Model Oligomers of siRNA and dsDNA

“…The influence of molecular architecture of dimeric surfactants on their ability to form stable complexes with nucleic acids is intensively studied, both in terms of the spacer group width, the length of alkyl chains, or the type of polar group. A wide spectrum of modulation possibilities of the architecture of gemini surfactant molecules allows for the selection of the right structure for the appropriate ability to bind nucleic acids [18,19,20,21,22,23,24,25]. Therefore, the aim of our research was to determine the complexation conditions and the structure of complexes formed by alkanediyl-α,ω-bis[(oxymethyl)dimethyldodecylammonium] chlorides and selected 21-base-pair nucleic acid (dsDNA and siRNA) oligomers.…”