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Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma
Lingling Ou1, Ting Sun1, Minyi Liu1
1The First Affiliated Hospital of Jinan University, Department of Stomatology, Guangzhou 510632, 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.
Insights
Graphene oxide-polyethylenimine (GO-PEI) effectively delivers a microRNA-214 (miR-214) inhibitor to treat oral squamous cell carcinoma (OSCC). This targeted therapy reduces tumor growth and metastasis by inhibiting miR-214.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Biology
Background:
- MicroRNAs (miRNAs) are key regulators in cancer development.
- miR-214 promotes oral squamous cell carcinoma (OSCC) progression and metastasis.
- Targeting miR-214 offers a potential therapeutic strategy for OSCC.
Purpose of the Study:
- To develop and evaluate graphene oxide-polyethylenimine (GO-PEI) complexes for targeted delivery of a miR-214 inhibitor.
- To assess the efficacy of GO-PEI-mediated miR-214 inhibition in OSCC cells and a xenograft mouse model.
Main Methods:
- Preparation of GO-PEI complexes loaded with a miR-214 inhibitor at varying N/P ratios.
- In vitro assessment of transfection efficiency in OSCC cell lines (Cal27, SCC9).
- In vivo evaluation of tumor inhibition in an OSCC xenograft mouse model via intratumoral injection.
Main Results:
- GO-PEI complexes efficiently delivered the miR-214 inhibitor into OSCC cells, controlling its intracellular release.
- Inhibition of miR-214 by GO-PEI-inhibitor decreased OSCC cell invasion and migration, and increased apoptosis by targeting PTEN and p53.
- The GO-PEI-miR-214 inhibitor complex significantly suppressed tumor volume growth in the xenograft model.
Conclusions:
- Functionalized GO-PEI demonstrates low toxicity and high potential for miRNA delivery in OSCC gene therapy.
- This approach offers a promising strategy for developing novel treatments for oral squamous cell carcinoma.
- Targeted delivery of miR-214 inhibitors using GO-PEI can effectively combat OSCC progression.
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