Microfluidic self-assembly of folate-targeted monomolecular siRNA-lipid nanoparticles

Nanoscale
R KrzysztońJoachim O Rädler

Abstract

Non-viral delivery of nucleic acids for therapies based on RNA interference requires a rational design and optimal self-assembly strategies. Nucleic acid particles need to be small, stable and functional in terms of selective cell uptake and controlled release of encapsulated nucleic acids. Here we report on small (∼38 nm) monomolecular nucleic acid/lipid particles (mNALPs) that contain single molecules of short double-stranded oligonucleotides covered by a tight, highly curved lipid bilayer. The particles consist of DOPE, DOTAP, DOPC and DSPE-PEG(2000) and are assembled with 21 bp double-stranded DNA or small interfering RNA by solvent exchange on a hydrodynamic-focusing microfluidic chip. In comparison to vortex mixing by hand this method increases the encapsulation efficiency by 20%, and yields particles with a narrower size distribution, negligible aggregate formation and high stability in blood plasma and serum. Modification of mNALPs with folate-conjugated PEG-lipids results in specific binding and uptake by epithelial carcinoma KB cells overexpressing folate receptors. Binding is significantly reduced by competitive inhibition using free folate and is not observed with non-targeted mNALPs, revealing high specificity. The...Continue Reading

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Citations

Oct 21, 2019·Pharmaceutical Nanotechnology·Sarah StreckArlene McDowell
Apr 8, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Brett A DuguayMarianna Kulka
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Aug 10, 2020·Advanced Drug Delivery Reviews·Sei YonezawaTomohiro Asai
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May 10, 2021·Biomaterials·Sarah J ShepherdMichael J Mitchell
May 21, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Zahid HussainMohammed A S Abourehab
Jul 20, 2021·Chemical Reviews·Yuebao ZhangYizhou Dong

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