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生物可降解二氧化硅纳米颗粒递送 MicroRNA-let-7c-5p 抑制人宫颈癌细胞增殖和迁移。

Delivery of MicroRNA-let-7c-5p by Biodegradable Silica Nanoparticles Suppresses Human Cervical Carcinoma Cell Proliferation and Migration.

出版信息

J Biomed Nanotechnol. 2020 Nov 1;16(11):1600-1611. doi: 10.1166/jbn.2020.2989.

Abstract

Human cervical cancer is the most common gynecological malignancy. The continuous development of nanotechnology has allowed the wide use of nanomaterials in cancer treatment. Nanoparticles can be used as gene carriers because of their surface effect and small-size effect. MicroRNA-let-7c-5p (miR-let-7c-5p) belongs to the let-7 family. Although it has been reported to exert a tumor suppressive effect in a variety of cancers, the exact role and mechanism of miR-let-7c-5p in the progression of cervical cancer are unclear. In this study, we synthesized flower-shaped SiO₂ -PEI nanoparticles with high pDNA/siRNA loading rates. This nanoparticle with miR-let-7c-5p-expressed plasmid could effectively transfer miR-let-7c-5p to human epithelial carcinoma (HeLa) cells. In addition, the combination of nanomaterials and gene therapy could inhibit the development of cancer under the conditions of extremely low cytotoxicity. These findings provided a new anticancer strategy based on F-SiO₂ -polyethyleneimine/miR-let-7c-5p (FSP-let-7c-5p)nanoparticles and indicated that miR-let-7c-5p/IGF-1R/PI3K/AKT and -catenin/SLUG could be used as new potential targets for the treatment of cervical cancer.

摘要

人宫颈癌是最常见的妇科恶性肿瘤。纳米技术的不断发展使得纳米材料在癌症治疗中得到广泛应用。由于纳米粒子具有表面效应和小尺寸效应,因此可以用作基因载体。微小 RNA-let-7c-5p(miR-let-7c-5p)属于 let-7 家族。尽管已有报道称其在多种癌症中具有肿瘤抑制作用,但 miR-let-7c-5p 在宫颈癌进展中的确切作用和机制尚不清楚。在这项研究中,我们合成了具有高 pDNA/siRNA 载量的花状 SiO₂-PEI 纳米粒子。这种表达 miR-let-7c-5p 的纳米粒子质粒能够有效地将 miR-let-7c-5p 转染到人上皮癌细胞中。此外,纳米材料与基因治疗的结合可以在极低的细胞毒性条件下抑制癌症的发展。这些发现为基于 F-SiO₂-聚亚乙基亚胺/miR-let-7c-5p(FSP-let-7c-5p)纳米粒子的新型抗癌策略提供了依据,并表明 miR-let-7c-5p/IGF-1R/PI3K/AKT 和-β-catenin/SLUG 可作为治疗宫颈癌的新的潜在靶点。

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