已发表论文

使用以生物可还原性聚乙烯亚胺包被氧化铁为基础的治疗诊断纳米颗粒来还原响应基因递送和磁共振成像

 

Authors Li D, Tang X, Pulli B, Lin C, Zhao P, Cheng J, Lv Z, Yuan X, Luo Q, Cai H, Ye M

Published Date July 2014 Volume 2014:9(1) Pages 3347—3361

DOI http://dx.doi.org/10.2147/IJN.S61463

Received 28 January 2014, Accepted 12 April 2014, Published 10 July 2014

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.
Keywords: nanoparticles, SSPEI, hTERT, disulfide, RNA interference, tumor, MR imaging