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.
Pharm Res. 2012 Jan;29(1):97-109. doi: 10.1007/s11095-011-0514-6. Epub 2011 Jul 6.
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.
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.
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.
These findings suggest that AMO-CLOSs represent a potential new approach for carrying anti-miRNA inhibitors for cancer therapy.
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。
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。
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。
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。