title: 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.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pulli
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Shanghai East Hospital, The Institute for Biomedical Engineering and Nanoscience, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Cai
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Tongji University, People's Republic of China.
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004220:Disulfides; D056945:Hep G2 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D011094:Polyethyleneimine / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology; D019098:Telomerase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D014162:Transfection / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D004220:Disulfides; D058185:Magnetite Nanoparticles; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D019098:Telomerase
keywords: MR imaging; RNA interference; SSPEI; disulfide; hTERT; nanoparticles; tumor