<p>Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma</p>

Abstract

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.

Promising Graphene-Based Nanomaterials and Their Biomedical Applications and Potential Risks: A Comprehensive Review

“…Furthermore, the terminal can also link with GBNs through surface functionalization to change the physical and chemical properties, reactivity, kinetics, and biological properties. A previous study reported that GO-PEI complexes encapsulate miR-214 inhibitors for the treatment of oral squamous cell carcinoma . GO modified by PAMAM dendrimers has a strong affinity to human breast cancer cell membrane and has no significant cytotoxicity .…”

The regulation of long non-coding RNA 00958 (LINC00958) for oral squamous cell carcinoma (OSCC) cells death through absent in melanoma 2 (AIM2) depending on microRNA-4306 and Sirtuin1 (SIRT1) in vitro

“…According to the analysis of differential expression genes in OSCC, we found that these genes are tightly correlated with p53 signaling pathway [ 32 ],which could regulate cell proliferation, apoptosis and autophagy [ 33 , 34 ]. Furthermore, the OSCC cell apoptotic levels could be significantly inhibited through targeting p53 [ 35 ]. Increased levels of p53 in the cytoplasm are involved in inhibiting autophagy [ 36 ].…”

Versatile carbon nanoplatforms for cancer treatment and diagnosis: strategies, applications and future perspectives

“…Electrostatic repulsion exists between GO and nucleic acid because they are both negatively charged, while polyetherimide (PEI) is a positively charged gene vector with a proton sponge effect, which can reduce the electrostatic repulsion between miRNAs and GO, thus improving the overall stability 61 . Ou et al firstly reported a gene therapy strategy for OSCC treatment by using positively charged PEI-functionalized GO to transport the inhibitor of miR-214 for suppressing OSCC cell proliferation 25 . In vitro and in vivo results showed that this nanocarrier could remarkably inhibit Cal27 and SCC9 tumor cell growth and migration by targeting phosphatase and tensin homolog (PTEN) and p53.…”