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

A.M. Chen, S.K. Nair, T.T. Thomas, T.J. Thomas and H. He
Rutgers Unverisity, Newark, US

Keywords:
gene delivery, gold nanoparticles, ODN condensation, DNA condensation, cancer therapy, dendrimer, nanoparticle

Abstract:
We demonstrated the formation of oligonucleotide nanoparticle in the presence of polypropylenimine dendrimers using total intensity light scattering as well as AFM and TEM. 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 property. Zeta potential analysis showed the positive charge of nanoparticles formed with G1-G3 dendrimers were significantly lower (5.5 – 6.5 mV) than those (12-18 mV) of particles formed with G4 and G5 dendrimers. These results indicate that the structure and charge density of the dendrimers exert an important effect on ON nanoparticle formation and cellular transport. Furthermore, we studied the condensation mechanism of the ON by PPI dendrimers and found that the PPI dendrimers first “zipped” the ON molecules by electrostatic interactions to form extended chains and the extended chains were then converted to the condensed spheroid and toroid-like nanoparticles. Finally, we report a novel condensing approach to reach a goal of high efficiency and low/nontoxic transport of high concentration ONs to cancer cells by using gold nanoparticles. This approach is very different from previous reported condensation of DNA by using Au nanoparticles in that in our approach, the gold nanoparticles acted as liable condensation “catalysts” to help the low generation dendrimers to effectively condense DNA while maintaining their non-toxic property.

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