Polymer genomics: shifting the gene and drug delivery paradigms
Polymer genomics: shifting the gene and drug delivery paradigms
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DOI：
10.1016/j.jconrel.2004.07.009
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发表时间：
2005-01-03
影响因子：
10.8
通讯作者：
Alakov, VY
中科院分区：
文献类型：
--
作者：
Kabanov, AV;Batrakova, EV;Alakov, VY
Pluronic是聚（环氧乙烷）和聚（环氧丙烷）的A-B-A两亲性嵌段共聚物，可以上调细胞中选定基因的表达，并改变癌症中对抗癌药物的遗传反应。两个关键的新发现进行了讨论，目前的药物和基因传递策略。首先，这些嵌段共聚物单独和与聚阳离子聚乙烯亚胺组合可以上调稳定转染细胞中报告基因的表达。这强调了所选择的合成聚合物通过增强改善的DNA递送到细胞中的机制来增强转基因表达的能力。第二，虽然单独使用时，Pluronic是“遗传良性的”，但当与抗肿瘤药物阿霉素联合使用时，它会大大改变对该药物的药物基因组学反应，并防止乳腺癌细胞中多药耐药性的发展。总的来说，这些研究提出需要对聚合物治疗的药物基因组学效应进行全面评估，以最大限度地提高临床结局，并了解聚合物药物和递送系统的药理学和毒理学效应。(c)2004 Elsevier B. V.保留所有权利。
Pluronic, the A-B-A amphiphilic block copolymers of poly(ethylene oxide) and poly(propylene oxide), can up-regulate the expression of selected genes in cells and alter genetic responses to antineoplastic agents in cancer. Two key new findings are discussed in relation to current drug and gene delivery strategies. First, these block copolymers alone and in combination with a polycation, polyethyleneimine, can up-regulate the expression of reporter genes in stably transfected cells. This underscores the ability of selected synthetic polymers to enhance transgene expression through a mechanism that augments improved DNA delivery into a cell. Second, although, when used alone, Pluronic is "genetically benign," when combined with an antineoplastic agent, doxorubicin, it drastically alters pharmacogenomic responses to this agent and prevents the development of multidrug resistance in breast cancer cells. Collectively, these Studies propose the need for a thorough assessment of pharmacogenomic effects of polymer therapeutics to maximize the clinical outcomes and understand the pharmacological and toxicological effects of polymer-based drugs and delivery systems. (c) 2004 Elsevier B.V. All rights reserved.