Journal
PHARMACEUTICAL RESEARCH
Volume 31, Issue 10, Pages 2685-2695Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-014-1366-7
Keywords
intracellular trafficking; lipid nanoparticles; miRNA; molecular beacon; siRNA
Funding
- NSF Nanoscale Science and Engineering Center (NSEC) [EEC-0914790]
- Chinese National 863 Project [2012AA020804]
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Purpose Understanding mechanisms of cellular uptake and intracellular release would enable better design of nanocarriers for delivery of nucleic acids such as siRNA and microRNA (miRNA). Method In this study, we investigated cellular pharmacokinetics of siRNA by co-encapsulating fluorescently labeled siRNA and molecular beacon (MB) in four different formulations of cationic lipid nanoparticles (LNPs). A miRNA mimic was also used as a probe for investigating cellular pharmacokinetics, which correlated well with RNAi activities. Results We tried to find the best LNP formulation based on the combination of DOTMA and DODMA. When the DOTMA/DODMA ratio was at 5/40, the LNP containing a luciferase siRNA produced the highest gene silencing activity. The superior potency of DOTMA/DODMA could be attributed to higher uptake and improved ability to facilitate siRNA release from endosomes subsequent to uptake. Conclusions Our findings may provide new insights into RNAi transfection pathways and have implications on cationic LNP design.
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