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Biomaterials. 2014 Aug;35(24):6534-42. doi: 10.1016/j.biomaterials.2014.04.057. Epub 2014 May 6.

Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging.

Author information

1
Department of Chemical Engineering, National Tsing Hua University, 101, Section 2, Kuang-Fu Road, Hsin-chu 30013, Taiwan, ROC.
2
Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou, 5 Fu-Shing Road, Kuei-Shan, Tao-Yuan 33305, Taiwan, ROC.
3
Department of Electrical Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kuei-Shan, Tao-Yuan 33302, Taiwan, ROC.
4
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.
5
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.
6
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.

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.

KEYWORDS:

Dendrimer; Drug delivery; MR imaging; Nanographene oxide; miRNA delivery

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