NANOSCALE: Pharmaceutically Engineered Nanoparticles for the Targeted Delivery of Plasmid DNA

NANOSCALE：用于靶向递送质粒 DNA 的药物工程纳米颗粒

• 批准号: 9986441
• 负责人: Russell Mumper
• 金额: $ 9.94万
• 依托单位: University of Kentucky Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-15 至 2002-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9986441&HistoricalAwards=false
• 关键词: NANOSCALE; Pharmaceutically; Engineered; Nanoparticles; Targeted

The investigators propose a novel method to pharmaceutically engineer solid nanoparticles in the size range of 5 to 50 nm containing plasmid DNA fornon-viral gene therapy applications. The method potentially overcomeslimitations of current non-viral gene delivery technology which uses positively-charged lipids or polymers to form larger, unstable complexeswith negatively-charged plasmid DNA in the size range of 100 to 1000 nm. Further, using the microemulsion precursor method to engineer solid nanoparticles, well-defined and uniform solid nanoparticles (5 to 50 nm)may be spontaneously and reproducibly made without the use of expensive or potentially damaging techniques involving high-torque mechanical mixing, microfluidization, homogenization, or milling. The proposed method involves the spontaneous formation of novel microemulsions wherein the dispersed droplets, which are typically 5 to 50 nm in diameter, are precursors for the formation of solid and stable nanoparticles. In addition to plasmid DNA, engineered nanoparticulate systems may contain many different materials for various medical and engineering applications such as nanomagnets and nanosensors.The specific goal of the project is to demonstrate that targeted solid nanoparticles containing plasmid DNA can be engineered from novel microemulsion precursors. The project has three specific aims, 1) demonstrate that plasmid DNA can be incorporated into a stable microemulsion and that stable solid nanoparticles (5-50 nm) containing plasmid DNA can be made from the microemulsion precursor, 2) characterize the solid nanoparticles (i.e., size, surface charge and porosity, DNA release and stability) and demonstrate that the solid nanoparticles are stable in biological fluids and can express a transgene in-vitro, and 3) incorporate a cell-specific ligand onto the surface of the solid nanoparticles and demonstrate surface recognition of the targeted nanoparticles.

研究人员提出了一种新的方法，在药物工程固体纳米颗粒的大小范围在5至50纳米包含质粒DNA用于非病毒基因治疗应用。该方法潜在地克服了当前非病毒基因传递技术的局限性，该技术使用带正电的脂质或聚合物与带负电的质粒DNA形成更大，不稳定的复合物，尺寸范围为100至1000纳米。此外，使用微乳液前驱体方法来设计固体纳米颗粒，定义良好且均匀的固体纳米颗粒（5至50纳米）可以自发且可重复地制造，而无需使用昂贵或潜在破坏性的技术，包括高扭矩机械混合，微流化，均质化或研磨。所提出的方法涉及新型微乳液的自发形成，其中分散的液滴通常直径为5至50纳米，是形成固体和稳定纳米颗粒的前体。除了质粒DNA，工程纳米粒子系统可能包含许多不同的材料，用于各种医学和工程应用，如纳米磁铁和纳米传感器。该项目的具体目标是证明含有质粒DNA的靶向固体纳米颗粒可以从新型微乳前体中工程化。该项目有三个具体目标，1)证明质粒DNA可以加入到稳定的微乳液中，并且可以从微乳液前体制备含有质粒DNA的稳定固体纳米颗粒（5-50 nm）， 2)表征固体纳米颗粒（即大小，表面电荷和孔隙度，DNA释放和稳定性），并证明固体纳米颗粒在生物流体中是稳定的，并且可以在体外表达转基因。3)将细胞特异性配体结合到固体纳米颗粒的表面，并证明目标纳米颗粒的表面识别。