Cationic gold microparticles for biolistic delivery of nucleic acids.

Here we report preparation and properties of positively charged gold microparticles, and their use for biolistic DNA delivery. Micron-sized gold microparticles were modified by building self-assembling polyethylenimine monolayers on their surfaces, which enabled their electrostatic interaction with negatively charged molecules such as DNA. One milligram of the surface-modified microparticles was able to bind directly to up to 3.5 microg of DNA, exceeding the 1 microg/mg limit of the conventional protocols. The binding showed no apparent dependency on DNA purity, size, or conformation. The interaction occurred over a broad range of pH values and salt concentrations, and was stable throughout the standard protocol for biolistic cartridge preparation. At the standard 1 microg dose, biological activity of the DNA biolistically delivered on the charge-modified gold was 25% higher than that delivered on conventional microparticles. Loading the charge-modified gold with more DNA stimulated proportionally higher gene expression. The charge-modified gold can be also used for delivery of small biological molecules such as siRNA. Tissue culture cells biolistically transfected with a LUC+ specific siRNA showed 80% reduction of Luc expression relative to those cells transfected with an irrelevant siRNA. Along with its superior properties as a DNA delivery vehicle, charge-modified gold offers a unique opportunity to deliver various DNA formulations in addition to traditional naked DNA.