Abstract

Small interfering RNAs (siRNAs) are a new class of medicine that shows the promising potential for diseases treats. However, due to degradation by endonucleases, large size and anionic charge, siRNA delivery is challenging and thus, delivery system is crucial. Lipid-based nanoparticles are mostly used for siRNA delivery. Since siRNAs in lipid-based nanoparticles are usually surrounded by a thin lipid bilayer, the availability of siRNA in cell cytosol is mainly dependent on the endocytosis mechanisms by which complex siRNA lipid-based nanoparticles enter into cells and that mechanisms dictate their intracellular fates, release and efficacy of siRNAs. This mini review provides a brief overview of mechanism of siRNA action, and the cellular entry mechanisms of lipid-based nanoparticles encapsulated with siRNAs and the perspectives for the rational design of nanoparticles in maximizing the efficacy of siRNA drugs.