Single-step microfluidic synthesis of transferrin-conjugated lipid nanoparticles for siRNA delivery

• DOI: 10.1016/j.nano.2016.09.014
• Publication Date: 2016-10-10T06:20:11Z
• Authors: Yujing Li; Robert J. Lee; Xueqin Huang; Yuhuan Li; Bingcong Lv; Tianpeng Wang; Yuhang Qi; Fei Hao; Jiahui Lu; Qingfan Meng; Lirong Teng; Yulin Zhou; Jing Xie; Lesheng Teng
• Keywords: Microfluidics; Transferrin; Humans; Nanoparticles; 02 engineering and technology; RNA, Small Interfering; 0210 nano-technology; Lipids

Microfluidic systems can accelerate clinical translation of nanoparticles due to their ability to generate nanoparticles in a well-controlled and reproducible manner. In this study, a single-step process based on microfluidic focusing (MF) was employed to synthesize transferrin-conjugated lipid nanoparticles (Tf-LNPs) and the method was compared with a multi-steps bulk mixing (BM) method. The results indicate that this single-step MF process enables rapid and efficient synthesis of Tf-LNPs, which were named Tf-LNPs-MF. Tf-LNPs-MF was shown to have a smaller size and more uniform structures compared to LNPs produced by multi-steps BM method (Tf-LNPs-BM). Furthermore, efficient cellular uptake of Tf-LNPs-MF in vitro as well as greater tumor inhibition in vivo proved that Tf-LNPs-MF had higher siRNA delivery efficiency in vitro and in vivo. Taken together, this single-step microfluidic synthesis significantly simplified the Tf-LNPs production and improved their drug delivery properties and may serve as a valuable tool for developing new cancer therapies.