Department of Pharmacology, ‡Department of Molecular and Cellular Biology, §Center for Drug Discovery, Dan L. Duncan Cancer Center, and Cardiovascular Research Institute, Baylor College of Medicine , Houston, Texas 77030, United States.
J Am Chem Soc. 2014 Jan 8;136(1):234-40. doi: 10.1021/ja408879b. Epub 2013 Dec 17.
Advancement of RNAi therapies is mainly hindered by the development of efficient delivery vehicles. The ability to create small size (<30 nm) oligonucleotide nanoparticles is essential for many aspects of the delivery process but is often overlooked. In this report, we describe diblock star polymers that can reproducibly complex double-stranded oligonucleotides into monodisperse nanoparticles with 15, 23, or 30 nm in diameter. The polymer-nucleic acid nanoparticles have a core-shell architecture with dense PEG brush coating. We characterized these nanoparticles using ITC, DLS, FRET, FCS, TIRF, and TEM. In addition to small size, these nanoparticles have neutral zeta-potentials, making the presented polymer architecture a very attractive platform for investigation of yet poorly studied polyplex size range for siRNA and antisense oligonucleotide delivery applications.
RNAi 疗法的发展主要受到高效递药载体的开发所阻碍。对于递药过程的许多方面来说，具有能够产生小尺寸（<30nm）寡核苷酸纳米颗粒的能力是至关重要的，但往往被忽视。在本报告中，我们描述了两亲星型聚合物，其可重复地将双链寡核苷酸组装成具有 15、23 或 30nm 直径的单分散纳米颗粒。聚合物-核酸纳米颗粒具有核壳结构，并且具有致密的 PEG 刷涂层。我们使用 ITC、DLS、FRET、FCS、TIRF 和 TEM 对这些纳米颗粒进行了表征。除了小尺寸之外，这些纳米颗粒还具有中性 zeta 电位，这使得所提出的聚合物结构成为研究 siRNA 和反义寡核苷酸递药应用中研究甚少的聚阳离子大小范围的极具吸引力的平台。
