Advancing Nonviral Gene Delivery: Lipid- and Surfactant-Based Nanoparticle Design Strategies

Abstract

Gene therapy is a technique utilized to treat diseases caused by missing, defective or overexpressing genes. Although viral vectors transfect cells efficiently, risks associated with their use limit their clinical applications. Nonviral delivery systems are safer, easier to manufacture, more versatile and cost effective. However, their transfection efficiency lags behind that of viral vectors. Many groups have dedicated considerable effort to improve the efficiency of nonviral gene delivery systems and are investigating complexes composed of DNA and soft materials such as lipids, polymers, peptides, dendrimers and gemini surfactants. The bottom-up approach in the design of these nanoparticles combines components essential for high levels of transfection, biocompatibility and tissue-targeting ability. This article provides an overview of the strategies employed to improve in vitro and in vivo transfection, focusing on the use of cationic lipids and surfactants as building blocks for nonviral gene delivery systems.

Lysine-functionalized nanodiamonds: synthesis, physiochemical characterization, and nucleic acid binding studies

“…A size in the range of 100-300 nm is considered optimal for producing efficient transfection. 49 In addition to appropriate size, the surface charge of transfection complexes also governs the intracellular delivery of transgenes, and an overall positive charge is desired in order to promote internalization across the negatively charged cell surface by means of favorable electrostatic interactions. 50 In order to optimize these parameters, the size and zeta potential of particles formed at various weight ratios of fNDs:pDNA and fNDs:siRNA were measured.…”

Calorimetric Investigations of Non-Viral DNA Transfection Systems

“…We have recently reported the results of an isothermal titration calorimetric (ITC) study of the interaction of DNA with transfection systems based upon a family of dimeric surfactants, more commonly known as gemini surfactants Yang et al, 2010;Donkuru et al, 2010). Gemini surfactants consist of two traditional surface active groups (i.e two hydrophobic chains and two polar headgroups) linked chemically by a spacer group.…”

“…m = 12) and the other has been replaced with a (pyren-6-yl)-hexyl group which has the same approximate length as a dodecyl group, but is significantly more hydrophobic in character (Wang et al, 2007b). The interaction between these pyrene-based gemini surfactants (Scheme 2B) and DNA using ITC (Donkuru et al, 2010), along with the 12-3-12 and 12-6-12 surfactants (for comparison), and marked differences in the interactions with DNA were observed ( Figure 5). The 2010 results for the interaction of the 12-3-12 and 12-6-12 with DNA showed a more complex interaction than that originally proposed in 2007, likely as a result of the difference in calorimeters used in the different studies.…”

Conditioning and Scaffolding of Chondrocytes: Smart Steps Towards Osteoarthritis Gene Therapy

“…Even in the field of viral vectors, attempts have been made to combine their application with immunomodulating agents (Ikeda et al, 2000), still obvious problems exist with this approach (Zhou et al, 2004). Similarly, in the area of non-viral gene transfer, researchers are generating new transfection methods/strategies with a number of new products becoming commercially available every year (Donkuru et al, 2010;Haag et al, 2009;Madeira et al, 2011). Yet, an ideal agent that satisfies the requirements for application with the relevant target cells for OA gene therapy is not in sight.…”