PEO-PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture.

PEO-PPO Diblock Copolymers Protect Myoblasts from Hypo-Osmotic Stress In Vitro Dependent on Copolymer Size, Composition, and Architecture.
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DOI:
10.1021/acs.biomac.7b00419
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发表时间:
2017-07-10
期刊:
影响因子:
6.2
通讯作者:
Hackel BJ
Hackel BJ
中科院分区:
化学2区
文献类型:
--
作者:
Kim M;Haman KJ;Houang EM;Zhang W;Yannopoulos D;Metzger JM;Bates FS;Hackel BJ

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泊洛沙姆188是聚(环氧乙烷)(PEO)和聚(环氧丙烷)(PPO)的三嵌段共聚物,可保护细胞膜免受各种应力。虽然存在许多嵌段共聚物变体,但对替代结构、组成和尺寸的评估很少。本文中,培养的鼠成肌细胞暴露于低渗休克和等渗恢复的应激,并且通过定量乳酸脱氢酶的释放来评价膜完整性。一组系统的PEO-PPO二嵌段和PEO-PPO-PEO三嵌段共聚物的比较评价表明,二嵌段结构可以在体外具有保护性。短PPO嵌段阻碍保护,在150 µM时需要>9个PPO单位进行保护,在14 µM时需要>16个单位。叔丁基端基的添加在降低的浓度下增强保护。当端基和PPO长度固定时,增加PEO长度可改善保护。这种系统的评价建立了一种新的体外筛选工具,用于评价膜密封两亲物,并提供了机制的见解,以指导未来的共聚物设计膜稳定在体内。
Poloxamer 188, a triblock copolymer of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), protects cellular membranes from various stresses. Though numerous block copolymer variants exist, evaluation of alternative architecture, composition, and size has been minimal. Herein, cultured murine myoblasts are exposed to the stresses of hypotonic shock and isotonic recovery, and membrane integrity was evaluated by quantifying release of lactate dehydrogenase. Comparative evaluation of a systematic set of PEO-PPO diblock and PEO-PPO-PEO triblock copolymers demonstrates that the diblock architecture can be protective in vitro. Short PPO blocks hinder protection with >9 PPO units needed for protection at 150 µM and >16 units needed at 14 µM. Addition of a tert-butyl end group enhances protection at reduced concentration. When the end group and PPO length are fixed, increasing the PEO length improves protection. This systematic evaluation establishes a new in vitro screening tool for evaluating membrane-sealing amphiphiles and provides mechanistic insight to guide future copolymer design for membrane stabilization in vivo.
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