title: Microfluidic assembly of lipid nanoparticles for delivery of antisense oligonucleotides.
abstract: 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.
authors.forename: Yulin
authors.initials: Y
authors.lastname: Zhou
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Meng
authors.forename: Tianqi
authors.initials: T
authors.lastname: Guo
authors.forename: Yige
authors.initials: Y
authors.lastname: Fu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Experimental Building, Jilin University, No. 2699, Qianjin Street, Changchun, 130012, China. xiejing@jlu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry*; D005434:Flow Cytometry; D006801:Humans; D007624:KB Cells; D044085:Microfluidics; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005229:Fatty Acids, Monounsaturated; D016376:Oligonucleotides, Antisense; D000644:Quaternary Ammonium Compounds; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane