Multifunctional Nanomedicine Platform for Cancer Specific Delivery of siRNA by Superparamagnetic Iron Oxide Nanoparticles-Dendrimer Complexes

Oleh      Taratula; Olga      Garbuzenko; Ronak      Savla; Y.      Andrew Wang; Huixin      He; Tamara      Minko

Abstract

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.

Keywords: 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