Title: Poly(propyleneimine) dendrimers as potential siRNA delivery nanocarrier: from structure to function

Authors: Oleh Taratula, Ronak Savla, Huixin He, Tamara Minko

Addresses: Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. ' Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA. ' Department of Chemistry, Rutgers, The State University of New Jersey 73 Warren Street, Newark, NJ 07102, USA. ' Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA

Abstract: The goal of the present investigation is to reveal the role of the Poly(propyleneimine) (PPI) dendrimer structure on the siRNA nanoparticles formation, facilitation of cell internalisation, and sequence specific knockdown of targeted genes. It was found that the higher generations of PPI dendrimers (G4 and G5) most effectively initiated the complexation of siRNA into discrete nanoparticles when compared with lower generations of dendrimers (G2 and G3) as determined by tapping mode atomic force microscopy and dynamic light scattering. The formulated siRNA-PPI dendrimer complexes provided for a dramatic enhancement in siRNA cellular internalisation and the marked knockdown of targeted mRNA expression in A549 human lung cancer cells. While the size and positive charge density of G5 is much larger than G4 dendrimers, provoking higher toxicity, G4 dendrimer shows the maximum efficacy terms of siRNA nanoparticles formation, intracellular siRNA internalisation, and sequence specific gene silencing.

Keywords: siRNA nanoparticles; PPI dendrimers; cellular internalisation; gene therapy; polypropylene imine dendrimers; human lung cancer cells; nanoparticle formation; gene silencing; nanotechnology.

DOI: 10.1504/IJNT.2011.037169

International Journal of Nanotechnology, 2011 Vol.8 No.1/2, pp.36 - 52

Available online: 30 Nov 2010 *

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