MicroRNAs (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 Fluc-3xPS 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
