Microfluidically (MF) synthesized lipid nanoparticles (LNPs) for antisense oligonucleotides (ODN) delivery
have been shown to be superior to those prepared by bulk mixing (BM). In this study, a 5-inlet MF chip was used to synthesize
LNPs loaded with LOR-2501, an antisense ODN targeting the ribonucleotide reductase R1 subunit. The size distribution
of ODN- LNPs was measured by dynamic light scattering. The cytotoxicity of ODN- LNPs was determined by
MTS assay. Gene silencing activity of ODN- LNPs was investigated by qRT-PCR and by Western blot. Results showed
that MF synthesis produced ODN-LNPs that have lower average size and polydispersity values. The highest antisense activity
was shown by LNs synthesized by the MF T2 chip, with downregulation of R1 mRNA by 32.5%. In conclusion, given
their simplicity, affordability and reproducibility, MF is an attractive method for synthesis of LNs for ODN delivery.
Keywords: Antisense oligonucleotide, cancer, microfluidics, nanoparticles, ribonucleotide reductase.
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