Oleh Taratula, Olga Garbuzenko, Ronak Savla, Y. Andrew Wang, Huixin He and Tamara Minko Pages 59 - 69 ( 11 )
The ability of Superparamagnetic Iron Oxide (SPIO) nanoparticles and Poly(Propyleneimine) generation 5 dendrimers (PPI G5) to cooperatively provoke siRNA complexation was investigated in order to develop a targeted, multifunctional siRNA delivery system for cancer therapy. Poly(ethylene glycol) (PEG) coating and cancer specific targeting moiety (LHRH peptide) have been incorporated into SPIO-PPI G5-siRNA complexes to enhance serum stability and selective internalization by cancer cells. Such a modification of siRNA nanoparticles enhanced its internalization into cancer cells and increased the efficiency of targeted gene suppression in vitro. Moreover, the developed siRNA delivery system was capable of sufficiently enhancing in vivo antitumor activity of an anticancer drug (Cisplatin). The proposed approach demonstrates potential for the creation of targeted multifunctional nanomedicine platforms with the ability to deliver therapeutic siRNA specifically to cancer cells in order to prevent severe adverse side effects on healthy tissues and in situ monitoring of the therapeutic outcome using clinically relevant imaging techniques.
SPIO nanoparticles, PPI dendrimer, siRNA, Cisplatin, LHRH peptide, imaging, tumor targeting, Magnetic Resonance Imaging, Superparamagnetic Iron Oxide, Polypropyleneimine Generation 5, 2,4,6-Trinitrobenzenesulphonic Acid, 1-octadecene, Sodium Dodecyl Sulfate, amphiphilic polymers, Dynamic Light Scattering, Atomic Force Microscope, luciferase, reverse transcription-polymerase chain reaction, Bicinchoninic Acid
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854–8020; USA.