Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging.

Abstract

Theranostic nanoparticles based on superparamagnetic iron oxide (SPIO) have a great promise for tumor diagnosis and gene therapy. However, the availability of theranostic nanoparticles with efficient gene transfection and minimal toxicity remains a big challenge. In this study, we construct an intelligent SPIO-based nanoparticle comprising a SPIO inner core and a disulfide-containing polyethylenimine (SSPEI) outer layer, which is referred to as a SSPEI-SPIO nanoparticle, for redox-triggered gene release in response to an intracellular reducing environment. We reveal that SSPEI-SPIO nanoparticles are capable of binding genes to form nano-complexes and mediating a facilitated gene release in the presence of dithiothreitol (5-20 mM), thereby leading to high transfection efficiency against different cancer cells. The SSPEI-SPIO nanoparticles are also able to deliver small interfering RNA (siRNA) for the silencing of human telomerase reverse transcriptase genes in HepG2 cells, causing their apoptosis and growth inhibition. Further, the nanoparticles are applicable as T2-negative contrast agents for magnetic resonance (MR) imaging of a tumor xenografted in a nude mouse. Importantly, SSPEI-SPIO nanoparticles have relatively low cytotoxicity in vitro at a high concentration of 100 μg/mL. The results of this study demonstrate the utility of a disulfide-containing cationic polymer-decorated SPIO nanoparticle as highly potent and low-toxic theranostic nano-system for specific nucleic acid delivery inside cancer cells.

• Authors: Dan Li, Xin Tang, Benjamin Pulli, Chao Lin, Peng Zhao, Jian Cheng, Zhongwei Lv, Xueyu Yuan, Qiong Luo, Haidong Cai, Meng Ye
• Journal: International journal of nanomedicine (Int J Nanomedicine) Vol. 9 Pg. 3347-61 ( 2014) ISSN: 1178-2013 [Electronic] New Zealand
• PMID: 25045265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Disulfides
• Magnetite Nanoparticles
• RNA, Small Interfering
• Polyethyleneimine
• Telomerase

Topics

• Animals
• Cell Survival (drug effects)
• Disulfides
• Hep G2 Cells
• Humans
• Magnetic Resonance Imaging (methods)
• Magnetite Nanoparticles (chemistry)
• Mice
• Mice, Nude
• Polyethyleneimine (chemistry)
• RNA, Small Interfering (genetics, pharmacology)
• Telomerase (analysis, genetics, metabolism)
• Transfection (methods)
• Xenograft Model Antitumor Assays