This goal of this project is to develop a new class of multi-layered nanoparticles that will be optimized for non-viral gene and oligonucleotide delivery. Each layer of the nanoparticles plays an important role in the efficient transport and delivery of nucleic acids to cells. Using self-assembly techniques, a metal nanocomposite particle that binds DNA at a high capacity and has a surface that is optimized for cell internalization will be fabricated. A unique characteristic of these delivery particles is that incident light excites a plasmon resonance and the particles intensely scatter light. Even at sizes below 100 nm, the particles image as colored point sources of light and can be individually identified in the interior of cells using dark field microscopy. By monitoring the position and DNA loading of the particles at each step in the complex nucleic acid delivery process, optimal particle formulations will be determined that maximize transfection efficiencies in cell lines that have been identified as promising targets for cancer gene therapy. ? ?
