Cellular Uptake Evaluation of Amphiphilic Polymer Assemblies: Importance of Interplay between Pharmacological and Genetic Approaches
Cellular Uptake Evaluation of Amphiphilic Polymer Assemblies: Importance of Interplay between Pharmacological and Genetic Approaches
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DOI：
10.1021/acs.biomac.9b01073
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发表时间：
2019-12-01
影响因子：
6.2
通讯作者：
Thayumanavan, S.
中科院分区：
文献类型：
--
作者：
Jiang, Ziwen;He, Huan;Thayumanavan, S.
了解材料的细胞摄取机制对于设计具有增强生物功能的材料具有重要意义。在此，我们报告了药理学和遗传学方法的相互作用，以尽量减少对细胞摄取机制的误解。两亲性聚合物的库被用作模型系统，以评估这种方法的相互作用的可靠性。为了探测两亲性聚合物的细胞摄取，我们利用正交端基标记策略在每个聚合物链上缀合一个荧光分子。与这些标记聚合物的方法相互作用的结果揭示了dynasore（一种众所周知的发动蛋白抑制剂）的脱靶效应。而不是发动蛋白，肌动蛋白被发现是一个必不可少的细胞组分在细胞摄取这些两亲性聚合物。我们的研究表明，在评估功能材料的内吞机制时，相互作用的药理学和遗传学方法的重要性，为了解未来治疗材料的细胞摄取提供了见解。
Understanding the cellular uptake mechanism of materials is of fundamental importance that would be beneficial for materials design with enhanced biological functions. Herein, we report the interplay of pharmacological and genetic approaches to minimize the possible misinterpretation on cellular uptake mechanism. A library of amphiphilic polymers was used as a model system to evaluate the reliability of such methodological interplay. To probe the cellular uptake of amphiphilic polymers, we utilized an orthogonal end-group labeling strategy to conjugate one fluorescent molecule on each polymer chain. The results from the methodological interplay with these labeled polymers revealed the off-target effects of dynasore, a well-known dynamin inhibitor. Instead of dynamin, actin was found to be an essential cellular component during the cellular uptake of these amphiphilic polymers. Our study demonstrates the importance of interplaying pharmacological and genetic approaches when evaluating the endocytic mechanism of functional materials, providing insights on understanding the cellular uptake of future therapeutic materials.