PEI-PEG-Chitosan Copolymer Coated Iron Oxide Nanoparticles for Safe Gene Delivery: synthesis, complexation, and transfection.
PEI-PEG-Chitosan Copolymer Coated Iron Oxide Nanoparticles for Safe Gene Delivery: synthesis, complexation, and transfection.
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DOI：
10.1002/adfm.200801844
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发表时间：
2009-07-24
影响因子：
19
通讯作者：
Zhang, Miqin
中科院分区：
文献类型：
--
作者：
Kievit, Forrest M.;Veiseh, Omid;Bhattarai, Narayan;Fang, Chen;Gunn, Jonathan W.;Lee, Donghoon;Ellenbogen, Richard G.;Olson, James M.;Zhang, Miqin
基因治疗提供了通过改变靶细胞的特定细胞功能来调节疾病的可能性。然而，尽管使用了独特的病毒和非病毒递送方法，但以最小的副作用将核酸有效地转运到靶细胞仍然是一个挑战。在这里，我们提出了一种非病毒纳米颗粒基因载体，它在体外和体内都证明了有效的基因传递和转染。纳米粒子系统(NP-CP-PEI)是由超顺磁性氧化铁纳米粒子(NP)制成的，它可以进行磁共振成像，并在天然多糖壳聚糖(CP)上接枝了由短链聚乙烯亚胺(PEI)和聚乙二醇(PEG)组成的新型共聚物(CP-PEI)，从而实现了对核酸的有效负载和保护。通过对三种不同表面化学性质的纳米粒子体系的比较研究，通过材料性质表征、DNA负载和转染分析以及毒性评估，阐明了该纳米粒子体系中各组成材料的功能。值得注意的是，NP-CP-PEI在C6异种移植小鼠模型中表现出无毒的毒性和高水平的表达，使其成为安全体内输送DNA进行基因治疗的潜在候选者。
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.
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影响因子：
10.8
作者：
Park, MR;Han, KO;Cho, CS
通讯作者：
Cho, CS
影响因子：
82.9
作者：
Medarova, Zdravka;Pham, Wellington;Moore, Anna
通讯作者：
Moore, Anna
DOI：
10.1016/j.ejpb.2007.02.024
发表时间：
2008-01-01
影响因子：
4.9
作者：
Petri-Fink, Alke;Steitz, Benedikt;Hofmann, Heinrich
通讯作者：
Hofmann, Heinrich
影响因子：
3.7
作者：
Fischer, D;Bieber, T;Kissel, T
通讯作者：
Kissel, T
影响因子：
4.7
作者：
Hong, Seungpyo;Leroueil, Pascale R.;Holl, Mark M. Banaszak
通讯作者：
Holl, Mark M. Banaszak