Li Yujing, Lee Robert J, Huang Xueqin, Li Yuhuan, Lv Bingcong, Wang Tianpeng, Qi Yuhang, Hao Fei, Lu Jiahui, Meng Qingfan, Teng Lirong, Zhou Yulin, Xie Jing, Teng Lesheng
School of Life Sciences, Jilin University, Changchun, Jilin, China.
School of Life Sciences, Jilin University, Changchun, Jilin, China; Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA.
Nanomedicine. 2017 Feb;13(2):371-381. doi: 10.1016/j.nano.2016.09.014. Epub 2016 Oct 6.
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.
微流控系统能够以可控且可重复的方式生成纳米颗粒，从而加速纳米颗粒的临床转化。在本研究中，采用了基于微流控聚焦（MF）的单步工艺来合成转铁蛋白共轭脂质纳米颗粒（Tf-LNPs），并将该方法与多步批量混合（BM）方法进行了比较。结果表明，这种单步MF工艺能够快速高效地合成Tf-LNPs，将其命名为Tf-LNPs-MF。与多步BM方法制备的LNP（Tf-LNPs-BM）相比，Tf-LNPs-MF的尺寸更小，结构更均匀。此外，Tf-LNPs-MF在体外具有高效的细胞摄取能力，在体内具有更强的肿瘤抑制作用，这证明Tf-LNPs-MF在体外和体内均具有更高的siRNA递送效率。综上所述，这种单步微流控合成方法显著简化了Tf-LNPs的生产过程，提高了其药物递送性能，可能成为开发新型癌症治疗方法的有价值工具。
