Purpose: Gene delivery relies on the delivery of a specific gene of interest to target cells. One of the major barriers to successful gene therapy is the transport of the DNA across cellular membranes. Synthetic gene therapy vectors rely on the use of various cationic agents (polymer, lipid, or surfactant) to condense and package DNA, and to facilitate its transport across cellular membranes. The purpose of this study was to examine the effect that surfactants used for gene delivery have on the structure of a simplistic model of an endosomal membrane.
Method: Model membranes were prepared from DPPC/Cholesterol or POPC/Cholesterol mixtures that were dissolved in Chloroform and deposited onto the surface of water contained in a Langmuir trough. Monolayers were treated with nanoparticles containing DNA, the neutral lipid DOPE, and gemini surfactant. Surface pressure was monitored using the Wilhelmy plate method while monolayers were compressed at a rate of 10 mm/min, providing the surface pressure vs. molecular area isotherm. Images of the monolayer at various surface pressures were obtained using a Brewster’s Angle Microscope.
Results: DOPE did not appear to participate significantly in the interaction between the surfactants and DNA. Both gemini surfactants were able to increase the fluidity of the model membranes.
Conclusions: The effect of gemini surfactants with respect to facilitating DNA delivery may involve not only condensing and packaging DNA, but also by playing an important role in the disruption of cellular membranes; specifically the disruption of endosomal membranes resulting in release of DNA into the cytosol.