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

Dan Li,1,* Xin Tang,2,* Benjamin Pulli,1 Chao Lin,2 Peng Zhao,2 Jian Cheng,2 Zhongwei Lv,1 Xueyu Yuan,1 Qiong Luo,1 Haidong Cai,1 Meng Ye1 1Department of Nuclear Medicine, Shanghai 10th People’s Hospital, 2Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience,...

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Autores principales:	Li D, Tang X, Pulli B, Lin C, Zhao P, Cheng J, Lv Z, Yuan X, Luo Q, Cai H, Ye M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7e5958fe899d4e2d8cf2e2200b0aa970
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spelling	oai:doaj.org-article:7e5958fe899d4e2d8cf2e2200b0aa9702021-12-02T05:39:45ZTheranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging1178-2013https://doaj.org/article/7e5958fe899d4e2d8cf2e2200b0aa9702014-07-01T00:00:00Zhttp://www.dovepress.com/theranostic-nanoparticles-based-on-bioreducible-polyethylenimine-coate-a17546https://doaj.org/toc/1178-2013 Dan Li,1,* Xin Tang,2,* Benjamin Pulli,1 Chao Lin,2 Peng Zhao,2 Jian Cheng,2 Zhongwei Lv,1 Xueyu Yuan,1 Qiong Luo,1 Haidong Cai,1 Meng Ye1 1Department of Nuclear Medicine, Shanghai 10th People’s Hospital, 2Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, People’s Republic of China *These authors contributed equally to this work 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 imagingLi DTang XPulli BLin CZhao PCheng JLv ZYuan XLuo QCai HYe MDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3347-3361 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li D Tang X Pulli B Lin C Zhao P Cheng J Lv Z Yuan X Luo Q Cai H Ye M Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
description	Dan Li,1,* Xin Tang,2,* Benjamin Pulli,1 Chao Lin,2 Peng Zhao,2 Jian Cheng,2 Zhongwei Lv,1 Xueyu Yuan,1 Qiong Luo,1 Haidong Cai,1 Meng Ye1 1Department of Nuclear Medicine, Shanghai 10th People’s Hospital, 2Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, People’s Republic of China *These authors contributed equally to this work 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
format	article
author	Li D Tang X Pulli B Lin C Zhao P Cheng J Lv Z Yuan X Luo Q Cai H Ye M
author_facet	Li D Tang X Pulli B Lin C Zhao P Cheng J Lv Z Yuan X Luo Q Cai H Ye M
author_sort	Li D
title	Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
title_short	Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
title_full	Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
title_fullStr	Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
title_full_unstemmed	Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
title_sort	theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/7e5958fe899d4e2d8cf2e2200b0aa970
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Theranostic nanoparticles based on bioreducible polyethylenimine-coated iron oxide for reduction-responsive gene delivery and magnetic resonance imaging

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