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Imaging Dendrimer-Grafted Graphene Oxide Mediated Anti-miR-21 Delivery With an Activatable Luciferase Reporter
Wang, Fu1; Zhang, Beilei2; Zhou, Lin1; Shi, Yaru1; Li, Zhiqiang1; Xia, Yuqiong1; Tian, Jie1,3
AbstractMicroRNAs (miRNAs) are a class of post-transcriptional gene regulators involved in various physiological processes including carcinogenesis, and they have emerged as potential targets for tumor theranostics. However, the employment of antisense oligonucleotides, termed anti-miRs, for antagonizing miRNA functions in vivo has largely been impeded by a lack of effective delivery carriers. Here, we describe the development of polyamidoamine (PAMAM) dendrimer and polyethylene glycol (PEG)-functionalized nanographene oxide (NGO) conjugate (NGO-PEG-dendrimer) for the efficient delivery of anti-miR-21 into non-small-cell lung cancer cells. To monitor the delivery of anti-miR-21 into cells and tumors, we also constructed an activatable luciferase reporter (Fluc-3xPS) containing three perfectly complementary sequences against miR-21 in the 3' untranslated region (UTR) of the reporter. Compared with bare dendrimer and Lipofectamine 2000 (Lipo2000), NGO-PEG-dendrimer showed considerably lower cytotoxicity and higher transfection efficiency. As demonstrated by in vitro bioluminescence imaging and Western blotting assays, NGO-PEG-dendrimer effectively delivered anti-miR-21 into the cytoplasm and resulted in the upregulation of luciferase intensity and PTEN target protein expression in a dose-dependent manner. Moreover, transfection with anti-miR-21 by NGO-PEG-dendrimer led to stronger inhibition of cell migration and invasion than did bare dendrimer or Lipo2000 transfection. The intravenous delivery of anti-miR-21 via NGO-PEG-dendrimer induced a significant increase in the bioluminescence signal within the Flue-UPS reporter-transplanted tumor areas. These results suggest that NGO-PEG-dendrimer could be an efficient and a potential nanocarrier for delivering RNA oligonucleotides. In addition, the strategy of combining NGO-PEG-dendrimer with an activatable luciferase reporter allows the image-guided monitoring of the delivery process, which can provide insights into the RNA-based cancer treatments.
KeywordMirna Delivery Graphene Oxide Dendrimer Luciferase Reporter Bioluminescence Imaging
WOS HeadingsScience & Technology ; Technology
Indexed BySCI
Funding OrganizationNational Natural Science Foundation of China(81301214 ; National Basic Research and Development Program of China (973 Program)(2013CB733803) ; 81571721)
WOS Research AreaScience & Technology - Other Topics ; Materials Science
WOS SubjectNanoscience & Nanotechnology ; Materials Science, Multidisciplinary
WOS IDWOS:000374274900020
Citation statistics
Cited Times:28[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorWang, Fu
Affiliation1.Xidian Univ, Sch Life Sci & Technol, Minist Educ, Engn Res Ctr Mol & Neuro Imaging, Xian 710071, Shaanxi, Peoples R China
2.Fourth Mil Med Univ, Tangdu Hosp, Dept Gynecol & Obstet, Xian 710038, Shaanxi, Peoples R China
3.Chinese Acad Sci, Inst Automat, Key Lab Mol Imaging, Beijing 100190, Peoples R China
Recommended Citation
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Wang, Fu,Zhang, Beilei,Zhou, Lin,et al. Imaging Dendrimer-Grafted Graphene Oxide Mediated Anti-miR-21 Delivery With an Activatable Luciferase Reporter[J]. ACS APPLIED MATERIALS & INTERFACES,2016,8(14):9014-9021.
APA Wang, Fu.,Zhang, Beilei.,Zhou, Lin.,Shi, Yaru.,Li, Zhiqiang.,...&Tian, Jie.(2016).Imaging Dendrimer-Grafted Graphene Oxide Mediated Anti-miR-21 Delivery With an Activatable Luciferase Reporter.ACS APPLIED MATERIALS & INTERFACES,8(14),9014-9021.
MLA Wang, Fu,et al."Imaging Dendrimer-Grafted Graphene Oxide Mediated Anti-miR-21 Delivery With an Activatable Luciferase Reporter".ACS APPLIED MATERIALS & INTERFACES 8.14(2016):9014-9021.
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