Oncotarget

Research Papers:

Microfluidic hydrodynamic focusing synthesis of polymer-lipid nanoparticles for siRNA delivery

Xueqin Huang, Robert J. Lee, Yuhang Qi, Yujing Li, Jiahui Lu, Qingfan Meng, Lesheng Teng _ and Jing Xie

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Oncotarget. 2017; 8:96826-96836. https://doi.org/10.18632/oncotarget.18281

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Abstract

Xueqin Huang1,2, Robert J. Lee1,3, Yuhang Qi1, Yujing Li1, Jiahui Lu1, Qingfan Meng1, Lesheng Teng1 and Jing Xie1

1School of Life Sciences, Jilin University, Changchun, Jilin 130023, China

2Department of Chemistry and Pharmacy, Zhuhai College of Jilin University, Zhuhai, Guangdong, 519041, China

3Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA

Correspondence to:

Lesheng Teng, email: tenglesheng@jlu.edu.cn

Jing Xie, email: xiejing@jlu.edu.cn

Keywords: microfluidic, polymer, lipid nanoparticles, siRNA delivery, cancer treatment

Received: December 12, 2016     Accepted: May 01, 2017     Published: May 30, 2017

ABSTRACT

Small interfering RNAs (siRNAs) are promising as therapeutics for intractable diseases such as cancer. However, efficient and safe delivery of siRNAs in vivo remains a challenge. Polymer-lipid hybrid nanoparticles (P/LNPs) have been evaluated for therapeutic delivery of siRNA. In this study, a microfluidic hydrodynamic focusing (MF) system was used to prepare P/LNPs loaded with VEGF siRNA. P/LNPs made by MF were smaller in particle size and had narrower size distribution compared to P/LNPs formed by bulk mixing (BM). MF-synthesized P/LNPs demonstrated low vehicle cytotoxicity and potent tumor cell inhibition in vitro. In addition, P/LNPs produced by the microfluidic chip exhibited prolonged blood circulation and increased AUC after i.v. injection compared to free siRNA. Furthermore, P/LNPs synthesized by MF induced greater down-regulation of VEGF mRNA and protein levels as well as greater tumor inhibition in a xenograft tumor model. Taken together, P/LNPs prepared by MF have been shown to be an effective and safe therapeutic siRNA delivery system for cancer treatment both in vitro and in vivo.


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