The effect of environmental pH on polymeric transfection efficiency
The effect of environmental pH on polymeric transfection efficiency
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DOI：
10.1016/j.biomaterials.2011.11.006
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发表时间：
2012-02-01
期刊：
影响因子：
14
通讯作者：
Bae, You Han
中科院分区：
文献类型：
--
作者：
Kang, Han Chang;Samsonova, Olga;Bae, You Han
尽管聚合物、聚合物复合体和细胞在聚合物制备和聚合物转染过程中暴露在不同的胞外和胞内pH环境中，但环境pH对聚合物转染的影响尚未被研究。本研究旨在通过调节转染液或培养液的pH值来了解环境pH对聚合转染体的影响。细胞外pH的变化通过复杂的因素影响聚合物的转导，如pH引起的聚合物特性(例如质子缓冲能力和电离)、多复合体特性(例如大小、表面电荷和解离)和细胞特性(例如细胞摄取、细胞周期相和细胞内pH环境)的变化。值得注意的是，酸性介质延迟了内吞作用、内体酸化、胞质释放和复合体的解离，从而对基因表达产生了负面影响。然而，酸性介质抑制了有丝分裂，减少了基因表达的稀释，从而提高了转染率。与pH 7.4相比，酸性培养基使基因表达降低1.6-7.7倍，而酸性培养基使基因表达效率提高2.1-2.6倍。培养基比转染液对聚合转染率的影响更大。了解细胞外pH在聚合基因转染过程中的影响，可能会激发新的策略，以确定有效和安全的聚合基因载体。(C)2011爱思唯尔有限公司。保留所有权利。
Although polymers, polyplexes, and cells are exposed to various extracellular and intracellular pH environments during polyplex preparation and polymeric transfection, the impact of environmental pH on polymeric transfection has not yet been investigated. This study aims to understand the influence of environmental pH on polymeric transfection by modulating the pH of the transfection medium or the culture medium. Changes in the extracellular pH affected polymeric transfection by way of complex factors such as pH-induced changes in polymer characteristics (e.g., proton buffering capacity and ionization), polyplex characteristics (e.g., size, surface charge, and decomplexation), and cellular characteristics (e.g., cellular uptake, cell cycle phases, and intracellular pH environment). Notably, acidic medium delayed endocytosis, endosomal acidification, cytosolic release, and decomplexation of polyplexes, thereby negatively affecting gene expression. However, acidic medium inhibited mitosis and reduced dilution of gene expression, resulting in increased transfection efficiency. Compared to pH 7.4 medium, acidic transfection medium reduced gene expression 1.6-7.7-fold whereas acidic culture medium enhanced transfection efficiency 2.1-2.6-fold. Polymeric transfection was affected more by the culture medium than by the transfection medium. Understanding the effects of extracellular pH during polymeric transfection may stimulate new strategies for determining effective and safe polymeric gene carriers. (C) 2011 Elsevier Ltd. All rights reserved.