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

Single-step microfluidic synthesis of transferrin-conjugated lipid nanoparticles for siRNA delivery
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用于 siRNA 递送的转铁蛋白缀合脂质纳米颗粒的一步微流体合成

DOI:
10.1016/j.nano.2016.09.014
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发表时间:
2017-02-01
影响因子:
5.4
通讯作者:
Teng, Lesheng
Teng, Lesheng
中科院分区:
医学2区
文献类型:
--
作者:
Li, Yujing;Lee, Robert J.;Teng, Lesheng

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微流体系统可以加速纳米颗粒的临床转化,因为它们能够以良好控制和可再现的方式生成纳米颗粒。在这项研究中,一个单步过程的基础上微流控聚焦(MF)合成转铁蛋白结合的脂质纳米粒子(Tf-LNPs)的方法进行了比较,与多步散装混合(BM)的方法。结果表明,这种一步MF方法能够快速有效地合成Tf-LNPs,其被命名为Tf-LNPs-MF。与多步BM法制备的LNP(Tf-LNPs-BM)相比,Tf-LNPs-MF显示出更小的尺寸和更均匀的结构。此外,Tf-LNPs-MF在体外的有效细胞摄取以及在体内更大的肿瘤抑制证明Tf-LNPs-MF在体外和体内具有更高的siRNA递送效率。总之,这种单步微流控合成显着简化了Tf-LNP的生产,并改善了其药物递送特性,可以作为开发新的癌症疗法的有价值的工具。(C)2016 Elsevier Inc. All rights reserved.
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. (C) 2016 Elsevier Inc. All rights reserved.