Controlled preparation of layered double hydroxide nanoparticles and their application as gene delivery vehicles

摘要

Layered double hydroxides (LDHs) have been known for many decades as catalyst and ceramic precursors, traps for anionic pollutants, catalysts, and additives for polymers, but they recently attracted attention as potential nano-sized carriers for therapeutic/bio-active molecules and genes. Among the many different nanoparticles that have been shown to facilitate gene and/or drug delivery, LDH nanoparticles are particularly well suited for this purpose due to their many desirable properties. In this research Mg_2Al(OH)_6NO_3 LDH nanoparticles of varying lateral sizes were synthesized by altering the synthesis conditions. The synthesis conditions particularly influencing the particle size distribution of the LDH suspensions are (a) the temperature during the co-precipitation step and (b) the duration and the temperature of the hydrothermal treatment. The association of these nanoparticles with plasmid DNA was studied and it was established that-in contrast to previously published reports-for the plasmid sizes used no significant intercalation occurs. The plasmids wrap around individual particles instead and aggregation of particles is observed. However, due to the observed strong interaction between LDH nanoparticles and DNA, the particles were nonetheless evaluated as transfection agents for mammalian cells. Considerable transfection efficiencies when transfecting adherent cell lines (i.e., HEK293T, NIH 3T3, COS-7, and CHO-K1) were observed, while the transfection of suspension CHO-S cells remained unsuccessful. This is attributed to the formation of aggregates upon DNA-LDH complex formation which settle on top of adherent cells but due to the constant agitation of suspension cultures not on the surface of e.g., CHO-S cells.