利用氧化石墨烯-聚亚乙基亚胺高效递送达 miRNA 抑制剂抑制口腔鳞状细胞癌。

Efficient miRNA Inhibitor Delivery with Graphene Oxide-Polyethylenimine to Inhibit Oral Squamous Cell Carcinoma.

机构信息

The First Affiliated Hospital of Jinan University, Department of Stomatology, Guangzhou 510632, People's Republic of China.

Stomatological Hospital of Southern Medical University, Department of Prosthodontics, Guangzhou 510260, People's Republic of China.

出版信息

Int J Nanomedicine. 2020 Mar 9;15:1569-1583. doi: 10.2147/IJN.S220057. eCollection 2020.

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.

背景

微 RNA（miRNA）被广泛认为是口腔鳞状细胞癌（OSCC）基因治疗的有前途的靶点。miR-214 已被确定为 OSCC 侵袭和转移的促进剂。

方法

制备氧化石墨烯-聚乙烯亚胺（GO-PEI）复合物，并在不同的 N/P 比下负载 miRNA 抑制剂。在 Cal27 和 SCC9 细胞中测试了 GO-PEI-抑制剂的转染效率。此外，通过瘤内注射在 OSCC 异种移植小鼠模型中测量了 GO-PEI-抑制剂的肿瘤抑制能力。

结果

在这里，我们表明 GO-PEI 复合物可有效将 miR-214 抑制剂递送至 OSCC 细胞，并控制 miR-214 抑制剂的细胞内释放。这些结果表明，GO-PEI-miR-214 抑制剂复合物通过靶向 PTEN 和 p53 有效抑制细胞内 miR-214，从而降低 OSCC 细胞的侵袭和迁移，并增加细胞凋亡。在异种移植小鼠模型中，GO-PEI-miR-214 抑制剂复合物显著阻止了肿瘤体积的生长。