Polyetherimide-grafted Fe₃O₄@SiO₂ nanoparticles as theranostic agents for simultaneous VEGF siRNA delivery and magnetic resonance cell imaging

Abstract

Engineering a safe and high-efficiency delivery system for efficient RNA interference is critical for successful gene therapy. In this study, we designed a novel nanocarrier system of polyethyleneimine (PEI)-modified Fe₃O₄@SiO₂, which allows high efficient loading of VEGF small hairpin (sh)RNA to form Fe₃O₄@SiO₂/PEI/VEGF shRNA nanocomposites for VEGF gene silencing as well as magnetic resonance (MR) imaging. The size, morphology, particle stability, magnetic properties, and gene-binding capacity and protection were determined. Low cytotoxicity and hemolyticity against human red blood cells showed the excellent biocompatibility of the multifunctional nanocomposites, and also no significant coagulation was observed. The nanocomposites maintain their superparamagnetic property at room temperature and no appreciable change in magnetism, even after PEI modification. The qualitative and quantitative analysis of cellular internalization into MCF-7 human breast cancer cells by Prussian blue staining and inductively coupled plasma atomic emission spectroscopy analysis, respectively, demonstrated that the Fe₃O₄@SiO₂/PEI/VEGF shRNA nanocomposites could be easily internalized by MCF-7 cells, and they exhibited significant inhibition of VEGF gene expression. Furthermore, the MR cellular images showed that the superparamagnetic iron oxide core of our Fe₃O₄@SiO₂/PEI/VEGF shRNA nanocomposites could also act as a T₂-weighted contrast agent for cancer MR imaging. Our data highlight multifunctional Fe₃O₄@SiO₂/PEI/VEGF shRNA nanocomposites as a potential platform for simultaneous gene delivery and MR cell imaging, which are promising as theranostic agents for cancer treatment and diagnosis in the future.

Keywords:

• core/shell nanoparticle
• PEI
• VEGF silence
• MR imaging
• theranostics

Acknowledgments

We would like to acknowledge financial support, in whole or in part, provided by the National Natural Science Foundation of China (numbers 81201192, 81101147, 31470959, 81471785, 11272083, and 31470906), the Sichuan Youth Science and Technology Foundation of China (numbers 2014JQ0008, 2010JQ0004), the Postdoctoral Science Foundation (2011M501406), and the China Postdoctoral Science Special Foundation (2012T50773). We would also like to thank Xuefeng Zhang from the National Research Council of Canada for his assistance in the experiments.

Disclosure

The authors report no conflicts of interest in this work.