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用于基因递送的普朗尼克嵌段共聚物。

Pluronic block copolymers for gene delivery.

作者信息

Kabanov Alexander, Zhu Jian, Alakhov Valery

机构信息

Department of Pharmaceutical Sciences, Center for Drug Delivery and Nanomedicine, College of Pharmacy, University of Nebraska Medical Center Omaha, Nebraska 68198, USA.

出版信息

Adv Genet. 2005;53:231-61.

Abstract

Amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide) called Pluronic or poloxamer are commercially available pharmaceutical excipients. They recently attracted considerable attention in gene delivery applications. First, they were shown to increase the transfection with adenovirus and lentivirus vectors. Second, they were shown to increase expression of genes delivered into cells using non-viral vectors. Third, the conjugates of Pluronic with polycations, were used as DNA-condensing agents to form polyplexes. Finally, it was demonstrated that they can increase regional expression of the naked DNA after its injection in the skeletal and cardiac muscles or tumor. Therefore, there is substantial evidence that Pluronic block copolymers can improve gene expression with different delivery routes and different types of vectors, including naked DNA. These results and possible mechanisms of Pluronic effects are discussed. At least in some cases, Pluronic can act as biological adjuvants by activating selected signaling pathways, such as NF-kappaB, and upregulating the transcription of the genes.

摘要

聚环氧乙烷和聚环氧丙烷的两亲性嵌段共聚物,即普朗尼克或泊洛沙姆,是市售的药用辅料。它们最近在基因递送应用中引起了相当大的关注。首先,已证明它们能提高腺病毒和慢病毒载体的转染效率。其次,已证明它们能提高使用非病毒载体递送至细胞内的基因的表达。第三,普朗尼克与聚阳离子的缀合物被用作DNA凝聚剂以形成多聚体。最后,已证明它们能在裸DNA注射到骨骼肌、心肌或肿瘤后提高其局部表达。因此,有大量证据表明普朗尼克嵌段共聚物可通过不同的递送途径和不同类型的载体(包括裸DNA)改善基因表达。本文讨论了这些结果以及普朗尼克效应的可能机制。至少在某些情况下,普朗尼克可通过激活选定的信号通路(如核因子κB)并上调基因转录来充当生物佐剂。

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