In this presentation, we will report our efforts to develop multifunctional non-viral condensing agent for gene delivery. We first demonstrated that five generations of (G-1 to G-5) of polypropylenimine (PPI) dendrimers were able to effectively condense both antisense oligonucleotide (ODN) and plasmid DNA into nanoparticles. Different generations of PPI dendrimers, with positively charged amino groups surrounding the surface, can be deemed as positively charged nanoparticles with different particle size. Confocal microscopic studies of fluorescein labelled ODN showed remarkable increase in the uptake of ODN complexed with PPI dendrimers compared to that of ODN alone. Based on this, we proposed that inorganic engineered nanoparticles, such as gold with sufficient positive charges on the surface are also be able to effectively condense DNA into nanoparticles for gene delivery. Our study using atomic force microscopy demonstrated that oxidized aniline-caped gold nanoparticles effectively condensed plasmid DNA into nanoparticles. However, DNA condensation by PPI G-4 dendrimer appears to follow a different pathway compared to that by the gold nanoparticle. To our knowledge, this is the first visualization of plasmid DNA condensed into nanoparticles by inorganic engineered nanoparticles. The gold nanoparticles, with unique optical and electrical properties, naturally provide high contrast in transmission electron microscopy (TEM) and could significantly enhance Raman signals. These properties of gold nanoparticles not only allow us to visualize the condensing agent in the final condensing products, they can also allow us to study the interaction between DNA and its condensing agent at a molecular structural level.
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