Polyethyleneimine-Functionalized Iron Oxide Nanoparticles for Systemic siRNA Delivery in Experimental Arthritis

Abstract

Aims: This study aimed to examine the efficacy of a nanocarrier (polyethyleneimine [PEI]-superparamagnetic iron oxide nanoparticle [SPIO]), composed of a core of iron oxide and a shell of PEI, in the systemic delivery of therapeutic siRNA to experimental arthritic joints. Materials & methods: PEI-SPIO/siRNA nanoparticles were synthesized and characterized in vitro. Nanoparticles were administered intravenously to arthritic rats to analyze cellular uptake, tissue distribution and the therapeutic effect of a siRNA against the IL-2/-15 receptor β chain (IL-2/IL-15Rβ). Results: PEI-SPIOs loaded with siRNA displayed negligible cytotoxicity, improved siRNA stability, efficient uptake by macrophages and the ability to induce specific gene silencing in vitro. PEI-SPIO-delivered siRNA accumulated easily in inflamed joints and was efficiently taken up by joint macrophages and T cells. Although IL-2/IL-15Rβ siRNA-loaded PEI-SPIOs alone were efficacious in the treatment of experimental arthritis, combination therapy with both PEI-SPIO/IL-2/IL-15Rβ siRNA and a magnetic field displayed an additive anti-inflammatory effect. Conclusion: PEI-functionalized SPIOs can be employed for systemic siRNA delivery in rheumatoid arthritis and enhanced therapeutic benefit can be achieved by the use of an external magnetic field.

Keywords::

• IL-2/IL-15Rb
• macrophage
• nanoparticle
• rheumatoid arthritis
• siRNA

Financial & competing interests disclosure

This work was supported by the National Natural Science Foundation of China (81071445) and National Key Technology Research and Development Program of China (2012BAI23B02). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Acknowledgements

The authors wish to thank F Miao for assistance in histologic analysis.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81071445) and National Key Technology Research and Development Program of China (2012BAI23B02). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.