Multilayer associates based on oligonucleotides and gold nanoparticles

The development of nanodevices for the efficient transport of therapeutic molecules is one of the most urgent problems of modern molecular medicine. Noncovalent agents for the delivery of nucleic acids (NA) including those based on gold nanoparticles (GNPs) represent an attractive alternative to covalent systems, since it is easier in this case to provide the controlled release of NA. We have demonstrated the possibility to create potentially biocompatible associates of GNPs containing alternating layers of oligonucleotides and other polymers as a promising platform for the delivery of oligonucleotides into living cells. The multilayer (five layers) coated GNPs can be assembled by the sequential treatment of gold nanoparticles with nonthiolated oligonucleotide (ON), thiolated carboxyl-polyethylene glycol (SH-PEG3000-COOH), and linear polyethyleneimine (PEI). We have developed an algorithm for the analysis of multilayer coated GNPs by gel electrophoresis, photon correlation spectroscopy, and transmission electron microscopy. The assembly of associates bearing two oligonucleotide layers and having a net positive surface charge has been described. Multilayer coated GNPs were shown not to degrade in the presence of a high concentration of the major blood protein, serum albumin.