title: Synthesis of Polymer-Lipid Nanoparticles by Microfluidic Focusing for siRNA Delivery.
abstract: Polyethylenimine (PEI) as a cationic polymer is commonly used as a carrier for gene delivery. PEI-800 is less toxic than PEI-25K but it is also less efficient. A novel nanocarrier was developed by combining PEI-800 with a pH-sensitive lipid to form polymer-lipid hybrid nanoparticles (P/LNPs). They were synthesized by microfluidic focusing (MF). Two microfluidic devices were used to synthesize P/LNPs loaded with VEGF siRNA. A series of P/LNPs with different particle sizes and distributions were obtained by altering the flow rate and geometry of microfluidic chips, and introducing sonication. Furthermore, the P/LNPs can be loaded with VEGF siRNA efficiently and were stable in serum for 12 h. Finally, P/LNPs produced by the microfluidic chip showed greater cellular uptake as well as down-regulation of VEGF protein level in both A549 and MCF-7 with reduced cellular toxicity. All in all, the P/LNPs produced by MF method were shown to be a safe and efficient carrier for VEGF siRNA, with potential application for siRNA therapeutics.
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. liyujing_jlu@126.com.
authors.forename: Yujing
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. M13843046552@163.com.|Department of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai 519041, China. M13843046552@163.com.
authors.forename: Xueqin
authors.initials: X
authors.lastname: Huang
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. lee.1339@osu.edu.|Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA. lee.1339@osu.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. qi13596940673@163.com.
authors.forename: Yuhang
authors.initials: Y
authors.lastname: Qi
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. 18844545746@163.com.
authors.forename: Kaikai
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. haofei123789@126.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Hao
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. steadyyangguang@163.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. lujh@jlu.edu.cn.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Lu
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. mengqf@jlu.edu.cn.
authors.forename: Qingfan
authors.initials: Q
authors.lastname: Meng
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. ls2012@jlu.edu.cn.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. xiejing@jlu.edu.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: School of Life Sciences, Jilin University, Qianjin Street No. 2699, Changchun 130012, China. tenglesheng@jlu.edu.cn.
authors.forename: Lesheng
authors.initials: L
authors.lastname: Teng
mesh_terms: D000072283:A549 Cells; D002470:Cell Survival; D015536:Down-Regulation; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D061986:MCF-7 Cells; D044085:Microfluidics / Q000295:instrumentation; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology*; D013010:Sonication; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008055:Lipids; D011108:Polymers; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D011094:Polyethyleneimine
keywords: lipid nanoparticles; microfluidic; polymer; siRNA