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载有抗 microRNA 寡核苷酸(AMOs)的固体脂质纳米颗粒,用于抑制人肺癌细胞中的 microRNA-21 功能。

Solid lipid nanoparticles loaded with anti-microRNA oligonucleotides (AMOs) for suppression of microRNA-21 functions in human lung cancer cells.

机构信息

Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.

出版信息

Pharm Res. 2012 Jan;29(1):97-109. doi: 10.1007/s11095-011-0514-6. Epub 2011 Jul 6.

Abstract

PURPOSE

Literature has highlighted the practical use of solid lipid nanoparticles (SLNs) in research, but few reports have combined SLNs with miRNA-based therapy. We aimed to prepare SLNs to load anti-miRNA oligonucleotide (AMO) for miRNA-based therapy in vitro.

METHODS

SLNs were employed to encapsulate AMO by a solvent diffusion method, and then the properties of AMO-CLOSs (cationic lipid binded oligonucleotide (AMO)-loaded SLNs) were characterized. We studied cellular uptake and activation properties of AMO-CLOSs in A549 cells, including antisense efficiency, cell migration and invasion.

RESULTS

AMO-CLOSs were 187 nm in size and 46.6 mV in zeta potential with an approximately toroid morphology in the TEM image. AMO-CLOSs uptake by A549 cells was increased significantly higher and more effective than free AMO. Further results demonstrated that AMO-CLOSs showed high antisense efficiency of microRNA-21 and subsequently decreased the proliferation, migration and invasion of tumor cells.

CONCLUSIONS

These findings suggest that AMO-CLOSs represent a potential new approach for carrying anti-miRNA inhibitors for cancer therapy.

摘要

目的

文献强调了固体脂质纳米粒(SLNs)在研究中的实际应用,但很少有报道将 SLNs 与基于 miRNA 的治疗结合使用。我们旨在制备 SLNs 以负载抗 miRNA 寡核苷酸(AMO)进行体外基于 miRNA 的治疗。

方法

采用溶剂扩散法将 AMO 包封在 SLNs 中,然后对阳离子脂质结合寡核苷酸(AMO)负载的 SLNs(AMO-CLOSs)的性质进行表征。我们研究了 AMO-CLOSs 在 A549 细胞中的细胞摄取和激活特性,包括反义效率、细胞迁移和侵袭。

结果

AMO-CLOSs 的粒径为 187nm,Zeta 电位为 46.6mV,TEM 图像呈近似环形形态。与游离 AMO 相比,AMO-CLOSs 被 A549 细胞摄取的显著增加且更有效。进一步的结果表明,AMO-CLOSs 表现出对 microRNA-21 的高反义效率,随后降低了肿瘤细胞的增殖、迁移和侵袭。

结论

这些发现表明,AMO-CLOSs 为携带抗 miRNA 抑制剂进行癌症治疗提供了一种潜在的新方法。

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