Importance of divalent cations in nanolipoplex gene delivery

Gene therapy is a promising therapeutic strategy to combat genetic or acquired diseases at their root cause rather than just treating symptoms. It is well recognised that there is an urgent need for non-toxic and efficient gene delivery vectors to fully exploit the current potential of gene therapy in molecular medicine. Cell-specific targeting of bioactive nucleotides is a prerequisite to attain the concentration of nucleic acids required for therapeutic efficacy in the target tissue. Many metal ions such as Mg2+, Mn2+, Ba2+ and, most importantly, Ca2+ have been demonstrated to have significant roles in gene delivery. These inorganic cations show low toxicity, good biocompatibility and promise for controlled delivery properties, thus presenting a new alternative to toxic and immunogenic carriers. Recently, inorganic nanoparticles alone, or in combination with a colloidal particulate system such as nanoliposome, an advanced approach to gene delivery, were found to exert a positive effect on gene transfer. In this report, the role of the divalent cations in nucleic acid delivery, particularly with respect to the potential improvement of transfection efficiency of nanolipoplexes, is reviewed.