期刊
BIOMATERIALS
卷 35, 期 24, 页码 6534-6542出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2014.04.057
关键词
Nanographene oxide; Dendrimer; Drug delivery; miRNA delivery; MR imaging
资金
- National Science Council of the Republic of China [NSC 102-2221-E-007-003-(102), NSC 102-2622-E-007-024-CC3, NSC 102-2314-B-182A-068-MY3, NSC 102-2120-M-182A-002-CC1, NHRI-EX103-10004NI, CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1]
- National Health Research Institutes of Taiwan [NSC 102-2221-E-007-003-(102), NSC 102-2622-E-007-024-CC3, NSC 102-2314-B-182A-068-MY3, NSC 102-2120-M-182A-002-CC1, NHRI-EX103-10004NI, CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1]
- Chang Gung Memorial Hospital [NSC 102-2221-E-007-003-(102), NSC 102-2622-E-007-024-CC3, NSC 102-2314-B-182A-068-MY3, NSC 102-2120-M-182A-002-CC1, NHRI-EX103-10004NI, CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1]
- Industrial Technology Research Institute [NSC 102-2221-E-007-003-(102), NSC 102-2622-E-007-024-CC3, NSC 102-2314-B-182A-068-MY3, NSC 102-2120-M-182A-002-CC1, NHRI-EX103-10004NI, CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1]
- National Tsing Hua University [NSC 102-2221-E-007-003-(102), NSC 102-2622-E-007-024-CC3, NSC 102-2314-B-182A-068-MY3, NSC 102-2120-M-182A-002-CC1, NHRI-EX103-10004NI, CMRPG3D0571, CMRPG3B1012, CMRPG392103, CORPG3C0041, CMRPG390071, CMRPG380571, 103A0045J2, 103N2753E1]
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 mu g/mL EPI) compared to Gd-NGO/EPI (3.4 mu g/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. (C) 2014 Elsevier Ltd. All rights reserved.
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