Functionalized graphene oxide as a nanocarrier for multiple suppressive miRNAs to inhibit human intrahepatic cholangiocarcinoma
Hui Yang,
Gaona Shi,
Chen Ge,
Jie Huang,
Lingfei Wan,
Zhaohai Wang,
Yunhui Liu,
Runqing Jia,
Minglian Wang,
Liming Zhang,
Zhijun Zhang,
Xinlong Yan
Affiliations
Hui Yang
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Gaona Shi
State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100050 China
Chen Ge
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Jie Huang
CAS Key Laboratory of Nano‐Bio Interface Division of Nanobiomedicine Suzhou Institute of Nano‐Tech & Nano‐bionics Chinese Academy of Sciences Suzhou 215123 China
Lingfei Wan
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Zhaohai Wang
Department of Hepatobiliary surgery Fifth Medical Center of Chinese PLA General Hospital Beijing 100039 China
Yunhui Liu
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Runqing Jia
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Minglian Wang
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Liming Zhang
Key Laboratory of Tropical Translational Medicine of Ministry of Education & Hainan Provincial Key Laboratory of Tropical Medicine Hainan Medical University Haikou 571101 China
Zhijun Zhang
CAS Key Laboratory of Nano‐Bio Interface Division of Nanobiomedicine Suzhou Institute of Nano‐Tech & Nano‐bionics Chinese Academy of Sciences Suzhou 215123 China
Xinlong Yan
College of Life Science and Bioengineering Faculty of Environmental and Life Sciences Beijing University of Technology Beijing 100124 China
Abstract The restoration of suppressed miRNAs is a promising therapeutic approach for treating tumors; however, efficient delivery remains a challenge. Herein, we aimed to develop a polyethylenimine (PEI) functionalized graphene oxide nanosheets (GO‐PEI) as a suppressive miRNA delivery system to treat human intrahepatic cholangiocarcinoma (ICC). We found that the GO‐PEI complex possessed excellent transfection efficacy and acceptable toxicity. Furthermore, using our miRNA array analysis and The Cancer Genome Atlas (TCGA) dataset, we selected four miRNAs (miR‐194‐5p, miR‐125b‐5p, miR‐122‐5p, and let‐7c‐5p) that are remarkably downregulated in ICC samples compared to that in adjacent tissues. The GO‐PEI complexed with the four miRNAs (GO‐PEI‐4miR) achieved a higher miRNA transfection efficiency than Lipo2000, as verified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) assays, immunofluorescence, and flow cytometry analyses. In addition, in vitro experiments revealed that GO‐PEI‐4miR remarkably restored the repressed miRNAs, thereby significantly repressing tumor sphere formation, colony formation, drug resistance, and markedly inhibiting the target genes of these miRNAs and cancer stem cell‐related markers. Furthermore, both tumor weights and bioluminescent imaging analysis indicated that the GO‐PEI‐4miR significantly reduced tumor formation in vivo. Taken together, these results demonstrate that GO‐PEI could be a potential delivery system for multiple repressive miRNAs in ICC therapy.
