title: Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging.
abstract: The delivery of anti-cancer therapeutics to tumors at clinically effective concentrations, while avoiding nonspecific toxicity, remains a major challenge for cancer treatment. Here we present nanoparticles of poly(amidoamine) dendrimer-grafted gadolinium-functionalized nanographene oxide (Gd-NGO) as effective carriers to deliver both chemotherapeutic drugs and highly specific gene-targeting agents such as microRNAs (miRNAs) to cancer cells. The positively charged surface of Gd-NGO was capable of simultaneous adsorption of the anti-cancer drug epirubicin (EPI) and interaction with negatively charged Let-7g miRNA. Using human glioblastoma (U87) cells as a model, we found that this conjugate of Let-7g and EPI (Gd-NGO/Let-7g/EPI) not only exhibited considerably higher transfection efficiency, but also induced better inhibition of cancer cell growth than Gd-NGO/Let-7g or Gd-NGO/EPI. The concentration of Gd-NGO/Let-7g/EPI required for 50% inhibition of cellular growth (IC50) was significantly reduced (to the equivalent of 1.3 μg/mL EPI) compared to Gd-NGO/EPI (3.4 μg/mL EPI). In addition, Gd-NGO/Let-7g/EPI could be used as a contrast agent for magnetic resonance imaging to identify the location and extent of blood-brain barrier opening and quantitate drug delivery to tumor tissues. These results suggest that Gd-NGO/Let-7g/EPI may be a promising non-viral vector for chemogene therapy and molecular imaging diagnosis in future clinical applications.
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsin-chu 30013, Taiwan, ROC.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, 5 Fu-Shing Road, Kuei-Shan, Tao-Yuan 33305, Taiwan, ROC.
authors.forename: Chiung-Yin
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsin-chu 30013, Taiwan, ROC.
authors.forename: Chih-Wen
authors.initials: CW
authors.lastname: Lin
authors.affiliation: Department of Electrical Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC.
authors.forename: Hao-Li
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, 5 Fu-Shing Road, Kuei-Shan, Tao-Yuan 33305, Taiwan, ROC.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Huang
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsin-chu 30013, Taiwan, ROC.
authors.forename: Shih-Sheng
authors.initials: SS
authors.lastname: Liao
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, 5 Fu-Shing Road, Kuei-Shan, Tao-Yuan 33305, Taiwan, ROC; School of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC.
authors.forename: Pin-Yuan
authors.initials: PY
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, 5 Fu-Shing Road, Kuei-Shan, Tao-Yuan 33305, Taiwan, ROC.
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, 5 Fu-Shing Road, Kuei-Shan, Tao-Yuan 33305, Taiwan, ROC; School of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC. Electronic address: kuochenwei@cgmh.org.tw.
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.affiliation: Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsin-chu 30013, Taiwan, ROC. Electronic address: ccma@che.nthu.edu.tw.
authors.forename: Chen-Chi M
authors.initials: CC
authors.lastname: Ma
mesh_terms: D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D015251:Epirubicin / Q000494:pharmacology; D005682:Gadolinium / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D008279:Magnetic Resonance Imaging; D035683:MicroRNAs / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010087:Oxides / Q000737:chemistry*; D056951:Photoelectron Spectroscopy; D055672:Static Electricity; D013818:Thermogravimetry; D014162:Transfection
chemical_list: D035683:MicroRNAs; D010087:Oxides; C487931:mirnlet7 microRNA, human; D015251:Epirubicin; D006108:Graphite; D005682:Gadolinium
keywords: Dendrimer; Drug delivery; MR imaging; Nanographene oxide; miRNA delivery