Pluronics and MDR reversal: an update.
Pluronics and MDR reversal: an update.
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DOI：
10.1021/mp500298q
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发表时间：
2014-08-04
影响因子：
4.9
通讯作者：
Kabanov AV
中科院分区：
文献类型：
--
作者：
Alakhova DY;Kabanov AV
多药耐药（MDR）仍然是癌症有效治疗的最大障碍之一。目前，临床上只有少数几种方法可以绕过耐多药，但成功率非常有限。在这篇综述中，我们描述了如何通过使用两亲嵌段共聚物的简单而有效的方法来克服MDR。聚环氧乙烷（PEO）和聚环氧丙烷（PPO）的三嵌段共聚物，排列成三嵌段结构PEO-PPO-PEO， Pluronics或“poloxamers”，引起了人们对给药领域的极大兴趣。先前的研究表明Pluronics使MDR癌细胞增敏，导致Dox、紫杉醇和其他药物的细胞毒性活性增加2-3个数量级。Pluronics还可以在体外和体内预防耐多药耐药的发展。此外，Dox/Pluronic制剂的临床研究结果令人鼓舞，这加强了对Pluronic在肿瘤中的作用进行深入了解的必要性。这些影响是非常全面的，并出现在质膜、线粒体水平上，并选择性地调节MDR癌细胞的基因表达。此外，最近已经证明Pluronics可以有效地消耗致瘤性内在耐药癌症干细胞（CSC）。有趣的是，耐多药的增敏和药物外排转运体的抑制对Pluronics不是特异性的或选择性的。其他两亲性聚合物在不同的实验模型中也显示出类似的活性。本文综述了Pluronic在耐多药致敏和预防方面的最新进展。
Multidrug resistance (MDR) remains one of the biggest obstacles for effective cancer therapy. Currently there are only few methods that are available clinically that are used to bypass MDR with very limited success. In this review we describe how MDR can be overcome by a simple yet effective approach of using amphiphilic block copolymers. Triblock copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), arranged in a triblock structure PEO-PPO-PEO, Pluronics or “poloxamers”, raised a considerable interest in the drug delivery field. Previous studies demonstrated that Pluronics sensitize MDR cancer cells resulting in increased cytotoxic activity of Dox, paclitaxel, and other drugs by 2–3 orders of magnitude. Pluronics can also prevent the development of MDR in vitro and in vivo. Additionally, promising results of clinical studies of Dox/Pluronic formulation reinforced the need to ascertain a thorough understanding of Pluronic effects in tumors. These effects are extremely comprehensive and appear on the level of plasma membranes, mitochondria, and regulation of gene expression selectively in MDR cancer cells. Moreover, it has been demonstrated recently that Pluronics can effectively deplete tumorigenic intrinsically drug-resistant cancer stem cells (CSC). Interestingly, sensitization of MDR and inhibition of drug efflux transporters is not specific or selective to Pluronics. Other amphiphilic polymers have shown similar activities in various experimental models. This review summarizes recent advances of understanding the Pluronic effects in sensitization and prevention of MDR.
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影响因子：
5.8
作者：
Alakhov, V;Klinski, E;Kabanov, A
通讯作者：
Kabanov, A
影响因子：
8
作者：
Chen Y;Sha X;Zhang W;Zhong W;Fan Z;Ren Q;Chen L;Fang X
通讯作者：
Fang X
影响因子：
4.9
作者：
Batrakova, Elena V.;Kelly, David L.;Kabanov, Alexander V.
通讯作者：
Kabanov, Alexander V.
影响因子：
4.9
作者：
Cambon, A.;Brea, J.;Mosquera, V.
通讯作者：
Mosquera, V.
影响因子：
9.9
作者：
Cha, Myoung-Hwa;Choi, Jiyeon;Han, Dong Keun
通讯作者：
Han, Dong Keun