(198an) Synthesis and Characterization of Hollow Gold Nanoparticles for Gene Delivery

Intracellular drug and gene delivery requires overcoming the barrier to endosome escape. Genetic materials and protein function in the cell cytosol, but typically < 2% of mRNA delivered via synthetic vectors reach their destination. Our strategy is to use liposomes coated with gold nanoparticles that can be triggered by picosecond pulses of near-infrared light to release biomolecules from the endosomes. The NIR light pulses generate vapor nanobubbles that mechanically rupture the liposome and endosome, releasing the mRNA to the cell cytosol. Here we describe two methods of attaching gold nanoparticles to liposomes to generate nanobubbles. The first method creates plasmon resonant hollow gold nanoshells (HGN) via a galvanic replacement reaction of gold salts with cubic silver template nanoparticles. These HGN are tethered to the liposomes via thiol terminated polyethylene glycol lipids on the liposome surface. In the second method, plasmon resonant gold nanoparticles are directly condensed onto the liposome exterior via reduction of chloroauric acid. We examine the threshold fluence and wavelength dependence necessary to rupture the liposomes and release mRNA into solution to determine an optimal mRNA delivery system.