Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma
Authors Ou L, Sun T, Liu M, Zhang Y, Zhou Z, Zhan X, Lu L, Zhao Q, Lai R, Shao L
Received 19 June 2019
Accepted for publication 2 January 2020
Published 9 March 2020 Volume 2020:15 Pages 1569—1583
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Dr Mian Wang
Lingling Ou,1 Ting Sun,1 Minyi Liu,1 Ye Zhang,1 Zhiying Zhou,1 Xiaozhen Zhan,1 Lihong Lu,1 Qingtong Zhao,1 Renfa Lai,1 Longquan Shao2
1The First Affiliated Hospital of Jinan University, Department of Stomatology, Guangzhou 510632, People’s Republic of China; 2Stomatological Hospital of Southern Medical University, Department of Prosthodontics, Guangzhou 510260, People’s Republic of China
Correspondence: Renfa Lai
The First Affiliated Hospital of Jinan University, No.613 West Huangpu Avenue, Guangzhou 510632, People’s Republic of China
Stomatological Hospital of Southern Medical University, No. 366 South Jiangnan Avenue, Guangzhou 510260, People’s Republic of China
Background: MicroRNAs (miRNAs) are widely believed to be promising targets for oral squamous cell carcinoma (OSCC) gene therapy. miR-214 has been identified as a promoter of OSCC aggression and metastasis.
Methods: Graphene oxide-polyethylenimine (GO-PEI) complexes were prepared and loaded with a miRNA inhibitor at different N/P ratios. The transfection efficiency of GO-PEI-inhibitor was tested in Cal27 and SCC9 cells. Moreover, the tumor inhibition ability of GO-PEI-inhibitor was measured in an OSCC xenograft mouse model by intratumoral injection.
Results: Here, we show that a GO-PEI complex efficiently delivers a miR-214 inhibitor into OSCC cells and controls the intracellular release of the miR-214 inhibitor. These results indicate that the GO-PEI-miR-214 inhibitor complex efficiently inhibited cellular miR-214, resulting in a decrease in OSCC cell invasion and migration and an increase in cell apoptosis by targeting PTEN and p53. In the xenograft mouse model, the GO-PEI-miR-214 inhibitor complex significantly prevented tumor volume growth.
Conclusion: This study indicates that functionalized GO-PEI with low toxicity has promising potential for miRNA delivery for the treatment of OSCC.
Keywords: oral squamous cell carcinoma, GO-PEI, miR-214 inhibitor, gene therapy
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