McAllister Karen, Sazani Peter, Adam Mirielle, Cho Moo J, Rubinstein Michael, Samulski Richard Jude, DeSimone Joseph M
Department of Chemistry, Campus Box 3290, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
J Am Chem Soc. 2002 Dec 25;124(51):15198-207. doi: 10.1021/ja027759q.
Polymeric nanogel vectors were developed for cellular gene and antisense delivery. Inverse microemulsion polymerization was utilized to synthesize biocompatible nanogels with controlled size, morphology, and composition. The chemical composition, size, polydispersity, stability, and swelling behavior of the nanogels were investigated by NMR, light scattering, transmission electron microscopy, and atomic force microscopy. The cell viability, uptake, and physical stability of nanogel-DNA complexes were evaluated under physiological conditions. Monodisperse nonionic and cationic nanogels were produced with controllable sizes ranging from 40 to 200 nm in diameter. The nanogels demonstrated extended stability in aqueous media and exhibited low toxicity in cell culture. Cationic nanogels formed monodisperse complexes with oligonucleotides and showed enhanced oligonucleotide uptake in cell culture. The nanogels synthesized in this study demonstrate potential utility as carriers of oligonucleotides and DNA for antisense and gene delivery.
聚合物纳米凝胶载体被开发用于细胞基因和反义核酸递送。采用反相微乳液聚合来合成具有可控尺寸、形态和组成的生物相容性纳米凝胶。通过核磁共振、光散射、透射电子显微镜和原子力显微镜研究了纳米凝胶的化学组成、尺寸、多分散性、稳定性和溶胀行为。在生理条件下评估了纳米凝胶-DNA复合物的细胞活力、摄取和物理稳定性。制备了直径在40至200nm范围内可控尺寸的单分散非离子和阳离子纳米凝胶。纳米凝胶在水性介质中表现出长期稳定性，并且在细胞培养中显示出低毒性。阳离子纳米凝胶与寡核苷酸形成单分散复合物，并在细胞培养中显示出增强的寡核苷酸摄取。本研究中合成的纳米凝胶证明了作为寡核苷酸和DNA载体用于反义核酸和基因递送的潜在用途。
