Novel Superparamagnetic Iron Oxide Nanoparticles for a Multifunctional Nanomedicine Platform

摘要

The rational for this study is to develop a multifunctional nanomedicine platform for siRNA delivery to cancerous tumors as well as to use magnetic resonance imaging (MRI) as a noninvasive strategy to monitor the drug therapy outcome. Therefore, we propose a multifunctional gene delivery vector by combining the magnetic properties of superparamagnetic iron oxide (SPIO) nanoparticles and their ability to package siRNAs into discrete complexes. The outer surface of SPIO was modified with two different polymer layers in tandem. The new design of nanoparticle surface modification allows sufficient binding strength to package large number of siRNAs and protect them in the delivery route. It also facilitates the siRNAs escape from endosomes to cytoplasm where they enter RNAi pathway. The prepared nanoparticles demonstrate high efficiency to provoke siRNAs complexation and largely facilitate their transfection into cancer cells. Moreover, to develop a specifically targeted, multifunctional siRNA delivery system with high transfection efficiency, the ability of SPIO nanoparticles and poly(propyleneimine) generation 5 dendrimer (PPI G5) to cooperatively provoke siRNA complexation was employed in the current study. In order to improve the efficiency of the designed vector, poly(ethylene glycol) (PEG) and receptor-binding ligands have been incorporated into SPIO/PPI G5/siRNA complexes to enhance serum stability and selective cellular internalization. The modified siRNA nanoparticles can sufficiently enhance the targeted cellular internalization and reduce the expression of the specific genes.