Condensation of Therapeutic Oligodeoxynucleotides and Plasmid DNA with PPI Dendrimers and PPI-Modified Gold Nanoparticles

摘要

We demonstrated the formation of oligodeoxynucleotide (ODN) nanoparticles in the presence of polypropylenimine (PPI) dendrimers using total intensity light scattering (TILS) and atomic force microscopy (AFM). Based on the interesting observations during the ODN condensation, two competitive condensation mechanisms were proposed, which are very different from the condensation pathways of high molecular weight DNA polymers. Confocal microscopic analysis showed that the nanoparticles formed with G4 and G5 dendrimers could undergo facile cellular uptake in a breast cancer cell line, MDA-MB-231, whereas particles formed with G1-G3 dendrimers lacked this ability. Nanoparticles formed with G1-G3 dendrimers showed significantly lower zeta potentials (5.2-6.5 mV) than those (12-18 mV) of particles formed with G4 and G5 dendrimers. These results indicate an important effect of both the size and surface charge density of the dendrimers on ODN nanoparticle formation and cellular transport. Finally, we report a novel condensing approach to reach a goal of high efficiency and low/nontoxic transport of high concentration DNAs to cancer cells by using low-generation PPI dendrimers with gold nanoparticles as labile catalyst.