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首页> 外文期刊>Materials science & engineering, C. Materials for Biogical applications >Propoxylation of cationic polymers provides a novel approach to controllable modulation of their cellular toxicity and interaction with nucleic acids
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Propoxylation of cationic polymers provides a novel approach to controllable modulation of their cellular toxicity and interaction with nucleic acids

机译:阳离子聚合物的丙氧基化为控制其细胞毒性和与核酸的相互作用提供了一种新颖的方法

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摘要

An effective chemical approach to modulation of biological interactions of cationic polymers was proposed and tested using polyethyleneimine (PEI) as a drug carrier. Branched 25 kDa PEI was modified in the reaction with propylene oxide (PO) to produce a series of propoxylated PEIs with NH groups grafted by single or oligomer PO units. Clear relationships between the propoxylation degree and biological effects, such as interaction with plasrnid DNA, hemolytic, cytotoxic, and pro-apoptotic activities were revealed for PEIs modified upon PO/NH molar ratio of 0.5, 0.75,1.0 and 3.0. The partial modification of available cationic centers up to 100% is predominantly accompanied by a significant gradual reduction in polycation adverse effects, while ability of complex formation with plasmid DNA is being preserved. Grafted PEI with 0.75 PO/NH ratio provides better protection from nuclease degradation and transfection activity compared with other modified PEIs. Revealed relationships contribute to the development of safe polymeric systems with controllable physicochemical properties and biological interactions. (C) 2016 Elsevier B.V. All rights reserved.
机译:提出了一种有效的化学方法来调节阳离子聚合物的生物相互作用,并使用聚乙烯亚胺(PEI)作为药物载体进行了测试。在与环氧丙烷(PO)的反应中,对支链25 kDa PEI进行了改性,以生成一系列带有NH基团的,由单个或低聚物PO单元接枝的丙氧基化PEI。对于PO / NH摩尔比为0.5、0.75、1.0和3.0修饰的PEI,丙氧基化程度与生物学效应之间存在明确的关系,例如与质粒DNA的相互作用,溶血,细胞毒性和促凋亡活性。有效阳离子中心的部分修饰最高达100%,主要伴随着聚阳离子不利影响的逐步减少,同时保留了与质粒DNA形成复合物的能力。与其他修饰的PEI相比,PO / NH比率为0.75的接枝PEI提供了更好的保护,使其免于核酸酶降解和转染活性。揭示的关系有助于开发具有可控物理化学性质和生物相互作用的安全聚合物系统。 (C)2016 Elsevier B.V.保留所有权利。

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