Multifunctional magnetic nanoparticles for targeted delivery.

Multifunctional magnetic nanoparticles for targeted delivery.
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用于靶向输送的多功能磁性纳米颗粒。

DOI:
10.1016/j.nano.2009.04.002
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发表时间:
2010-02
影响因子:
5.4
通讯作者:
Mohapatra, Shyam
Mohapatra, Shyam
中科院分区:
医学2区
文献类型:
--
作者:
Kumar, Arun;Jena, Prasanna K.;Behera, Sumita;Lockey, Richard F.;Mohapatra, Subhra;Mohapatra, Shyam

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与治疗相关的主要问题是无法将药物递送到身体的特定部位而不引起非特异性毒性。磁性纳米粒子及其在体内特定部位的安全运输和浓缩技术的发展将成为体内基因/药物治疗的有力工具。此外,如果用抗体、蛋白质或配体修饰药物,则可以进一步改善药物的体外递送。对于体内实验,磁性纳米颗粒与表达GFP的质粒DNA缀合,然后用壳聚糖包被。这些粒子通过尾静脉注射到小鼠体内,并通过25高斯或2kA-kA/m的外部磁体引导到心脏和肾脏。这些颗粒集中在小鼠的肺、心脏和肾脏中,并监测这些部位中GFP的表达。通过全身荧光成像可视化特定位置中GFP的表达,并通过透射电子显微镜证实这些颗粒在指定身体位置中的浓度。在另一个模型系统中,我们使用心房利钠肽(ANP)和癌胚抗原(CEA)抗体偶联到壳聚糖涂层的磁性纳米颗粒体外靶向细胞。目前的工作表明,简单的外部磁场是将药物靶向体内特定部位所必需的,而不需要使纳米颗粒功能化。然而,在功能化纳米颗粒上使用外部磁体的磁性靶向选择可以证明是一种更有效的药物递送手段。
A major problem associated with therapy is the inability to deliver pharmaceuticals to a specific site of the body without causing nonspecific toxicity. Development of magnetic nanoparticles and techniques for their safe transport and concentration in specific sites in the body would constitute a powerful tool for gene/drug therapy in vivo. Furthermore, drug delivery in vitro could improve further if the drugs were modified with antibodies, proteins or ligands. For in vivo experiments, magnetic nanoparticles were conjugated with plasmid DNA expressing GFP and then coated with chitosan. These particles were injected into mice through tail vein and directed to heart and kidney by means of external magnets of 25 gauss or 2kA –kA/m. These particles were concentrated in the lungs, heart, and kidney of mice and the expression of GFP in these sites were monitored. The expression of GFP in specific locations was visualized by whole-body fluorescent imaging and the concentration of these particles in the designated body locations was confirmed by transmission electron microscopy. In another model system, we used atrial natriuretic peptide (ANP) and Carcino Embryonic Antigen (CEA) antibodies coupled to the chitosan coated magnetic nanoparticles to target cells in vitro. The present work demonstrates that a simple external magnetic field is all that is necessary to target a drug to a specific site inside the body without the need to functionalize the nanoparticles. However, the option to use magnetic targeting with external magnets on functionalized nanoparticles could prove as a more efficient means of drug delivery.
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