Magnetically guided survivin-siRNA delivery and simultaneous dual-modal imaging visualization based on Fe3O4@mTiO2 nanospheres for breast cancer

Abstract

Small interfering RNA (siRNA) has great potential for gene therapy of breast cancer. The development of multifunctional nanocarriers possessing the targeted ability and multimodal imaging function is important to increase siRNA transfection efficiency and to visualize the delivery events. Herein, we demonstrate flavin mononucleotide (FMN) and polyethylenimine (PEI) modified Fe₃O₄@mTiO₂ nanoparticles (Fe₃O₄@mTiO₂/FMN-PEI) as novel magnetic fluorescent siRNA delivery systems. The system has magnetic targeting, magnetic resonance imaging (MRI), optical imaging, and high siRNA binding ability. Survivin-siRNA delivered by this system can effectively enter into MCF-7 cells, which can be further enhanced by exerting an external magnetic field. More importantly, the siRNA delivery events including the location, trafficking, distribution, and release, can be visualized by MRI and optical imaging. Gene silencing by survivin-siRNA can cause significant protein knockdown (96%) and considerable cell apoptosis (30%), indicating the usefulness of Fe₃O₄@mTiO₂/FMN-PEI as a siRNA delivery system.