Multifunctional Superparamagnetic Nanoparticles: From Synthesis to siRNA Delivery

Background: Targeted delivery of small interfering RNA (siRNA) to the specific tumor tissues and cells is the key challenge in the development of RNA interference as a therapeutic application. Methods: To target breast cancer, we developed a cationic nanoparticle as a therapeutic delivery system. The successful synthesis of the magnetic nanoparticles modified by polyaspartate (PAA) and polyethyleneimine (PEI) was confirmed using fourier transform infrared (FT-IR) measurements. The designed nanoparticle has been characterized evaluating its size and charge before and after nanoplex formation with siRNA. Results: The designed nanoparticle could effectively form nanoplex with siRNA in 2:1 w/w ratio. Survivin siRNA was used to suppress the antiapoptotic gene, survivin, in MCF-7 cells. According to the importance of combinational therapy, Mitoxantrone (MTX) was used as a chemotherapeutic agent as well. The multifunctional nanoparticles have been successfully entered into about 63% of the MCF-7 cells shown via microscopic and flowcytometric methods. This effective cellular uptake led to the cell apoptosis. Down regulation of survivin was determined in mRNA and protein levels using Real Time PCR and western blotting, respectively. Conclusion: Gathering all obtained data, it was concluded that Fe3O4-PAA-PEI nanoparticles can deliver siRNA effectively into the cytoplasm of the MCF-7 breast cancer cells and induce apoptosis.