Kievit Forrest M, Veiseh Omid, Bhattarai Narayan, Fang Chen, Gunn Jonathan W, Lee Donghoon, Ellenbogen Richard G, Olson James M, Zhang Miqin
Department of Materials Science & Engineering, University of Washington, Seattle, WA 98195 (USA).
Adv Funct Mater. 2009 Jul 24;19(14):2244-2251. doi: 10.1002/adfm.200801844.
Gene therapy offers the potential of mediating disease through modification of specific cellular functions of target cells. However, effective transport of nucleic acids to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. Here we present a non-viral nanoparticle gene carrier that demonstrates effective gene delivery and transfection both in vitro and in vivo. The nanoparticle system (NP-CP-PEI) is made of a superparamagnetic iron oxide nanoparticle (NP), which enables magnetic resonance imaging, coated with a novel copolymer (CP-PEI) comprised of short chain polyethylenimine (PEI) and poly(ethylene glycol) (PEG) grafted to the natural polysaccharide, chitosan (CP), which allows efficient loading and protection of the nucleic acids. The function of each component material in this nanoparticle system is illustrated by comparative studies of three nanoparticle systems of different surface chemistries, through material property characterization, DNA loading and transfection analyses, and toxicity assessment. Significantly, NP-CP-PEI demonstrates an innocuous toxic profile and a high level of expression of the delivered plasmid DNA in a C6 xenograft mouse model, making it a potential candidate for safe in vivo delivery of DNA for gene therapy.
基因治疗通过修饰靶细胞的特定细胞功能，为介导疾病治疗提供了可能。然而，尽管使用了独特的病毒和非病毒递送方法，但将核酸有效输送到靶细胞并使其副作用最小化仍然是一个挑战。在此，我们展示了一种非病毒纳米颗粒基因载体，其在体外和体内均表现出有效的基因递送和转染能力。该纳米颗粒系统（NP-CP-PEI）由超顺磁性氧化铁纳米颗粒（NP）构成，它能够实现磁共振成像，表面包覆有一种新型共聚物（CP-PEI），该共聚物由短链聚乙烯亚胺（PEI）和接枝到天然多糖壳聚糖（CP）上的聚乙二醇（PEG）组成，可实现核酸的高效装载和保护。通过对三种具有不同表面化学性质的纳米颗粒系统进行比较研究，借助材料特性表征、DNA装载和转染分析以及毒性评估，阐明了该纳米颗粒系统中各组成材料的功能。值得注意的是，在C6异种移植小鼠模型中，NP-CP-PEI表现出无毒的毒性特征以及所递送质粒DNA的高水平表达，使其成为基因治疗中用于安全体内递送DNA的潜在候选物。
