San-Jun Shi1, Zhi-Rong Zhong, Jie Liu, Zhi-Rong Zhang, Xun Sun, Tao Gong. 1. 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.
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.
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.
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