Colloidal aggregation affects the efficacy of anticancer drugs in cell culture.
Colloidal aggregation affects the efficacy of anticancer drugs in cell culture.
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DOI：
10.1021/cb300189b
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发表时间：
2012-08-17
影响因子：
4
通讯作者：
Shoichet, Brian K.
中科院分区：
文献类型：
--
作者：
Owen, Shawn C.;Doak, Allison K.;Wassam, Pascal;Shoichet, Molly S.;Shoichet, Brian K.
许多小分子，包括生物活性分子和批准的药物，在微摩尔浓度下在水溶液中自发形成胶体聚集体。虽然它被广泛接受，聚集导致的文物在筛选可溶性蛋白质的配体，胶体形成的影响，在基于细胞的测定还没有研究。在这里，发现七种抗癌药物和一种诊断试剂在生化缓冲液和细胞培养基中形成胶体。在基于细胞的测定中，与单体形式相比，胶体形式的三种药物的抗增殖活性大幅降低;新的配制方法确保了溶液中药物胶体与药物单体的存在。我们还发现，伊文思蓝，一种经典用于测量血管渗透性并证明实体瘤中“增强的渗透性和保留（EPR）效应”的染料，形成吸附白蛋白的胶体，而不是旧文献中提出的相反。
Many small molecules, including bioactive molecules and approved drugs, spontaneously form colloidal aggregates in aqueous solution at micromolar concentrations. Though it is widely accepted that aggregation leads to artifacts in screens for ligands of soluble proteins, the effects of colloid formation in cell-based assays have not been studied. Here, seven anticancer drugs and one diagnostic reagent were found to form colloids in both biochemical buffer and in cell culture media. In cell-based assays, the antiproliferative activities of three of the drugs were substantially reduced when in colloidal form as compared to monomeric form; a new formulation method ensured the presence of drug colloids versus drug monomers in solution. We also found that Evans Blue, a dye classically used to measure vascular permeability and to demonstrate the “enhanced permeability and retention (EPR) effect” in solid tumors, forms colloids that adsorb albumin, as opposed to older literature that suggested the reverse.
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影响因子：
7.3
作者：
Jadhav A;Ferreira RS;Klumpp C;Mott BT;Austin CP;Inglese J;Thomas CJ;Maloney DJ;Shoichet BK;Simeonov A
通讯作者：
Simeonov A
影响因子：
7.3
作者：
Shoichet, Brian K.
通讯作者：
Shoichet, Brian K.
影响因子：
7.3
作者：
McGovern, SL;Helfand, BT;Shoichet, BK
通讯作者：
Shoichet, BK
影响因子：
--
作者：
Coan, Kristin E. D.;Shoichet, Brian K.
通讯作者：
Shoichet, Brian K.
影响因子：
16.6
作者：
Wienken, Christoph J.;Baaske, Philipp;Duhr, Stefan
通讯作者：
Duhr, Stefan