Vert M, Domurado D
Centre de Recherche sur les Biopolymères Artificiels, UMR CNRS 5473, University Montpellier I, Faculty of Pharmacy, France.
J Biomater Sci Polym Ed. 2000;11(12):1307-17. doi: 10.1163/156856200744345.
In the literature, many papers deal with the behavior of proteins in aqueous media in the presence of poly(ethylene glycol) (PEG) molecules or poly(ethylene oxide) (PEO) segments, physically adsorbed onto, or covalently attached to, macromolecules or to solid surfaces. In particular, it is well known that PEO segments make foreign materials stealthy, i.e. they are much less detected by the immune system either through humoral reactions or, at the cell level, through opsonins. Revisiting the literature led us to challenge the largely accepted opinion that the decreased recognition of PEO segment-bearing foreign macromolecules and particles by the mononuclear phagocyte system is primarily the consequence of the repulsion of all blood proteins by PEG segments through the excluded volume effect. This challenge is based on the finding that albumin and PEG are compatible in phosphate-buffered saline at room temperature and at concentrations comparable to those measured by others on the surface of PEO segment-bearing species, whereas fibrinogen and PEG phase-separated and were incompatible despite the much lower concentration of the latter protein. According to literature and to these observations, it is proposed that the stealth effect induced by PEO segments is primarily due to the compatibility between PEO segments of intermediate molar mass and albumin, thus rendering PEO-bearing macromolecules or surfaces to look like native albumin. Under such conditions, the hospitality offered by PEG macromolecules or PEO segments to albumin, the dominant plasma protein, results in a 'chameleon' effect that prevents the activation of other PEG-compatible or -incompatible plasma proteins or cells involved in foreign body recognition and elimination. PEG with molar masses > or = 8000 did not accommodate albumin in agreement with the excluded volume phenomenon.
在文献中，许多论文探讨了在聚乙二醇（PEG）分子或聚环氧乙烷（PEO）链段存在的情况下，蛋白质在水性介质中的行为，这些分子或链段物理吸附或共价连接到大分子或固体表面上。特别地，众所周知，PEO链段能使异物具有隐形性，即它们通过体液反应或在细胞水平上通过调理素被免疫系统检测到的可能性要小得多。重新审视文献使我们对一个被广泛接受的观点提出质疑，即单核吞噬细胞系统对带有PEO链段的外来大分子和颗粒识别能力的降低主要是由于PEG链段通过排阻体积效应排斥所有血液蛋白的结果。这一质疑基于以下发现：在室温下，白蛋白和PEG在磷酸盐缓冲盐水中是相容的，且浓度与其他人在带有PEO链段的物种表面测得的浓度相当，而纤维蛋白原和PEG会发生相分离且不相容，尽管后者蛋白质的浓度要低得多。根据文献和这些观察结果，有人提出PEO链段诱导的隐形效应主要是由于中等摩尔质量的PEO链段与白蛋白之间的相容性，从而使带有PEO的大分子或表面看起来像天然白蛋白。在这种情况下，PEG大分子或PEO链段对占主导地位的血浆蛋白白蛋白的亲和性会产生一种“变色龙”效应，从而阻止参与异物识别和清除的其他与PEG相容或不相容的血浆蛋白或细胞被激活。摩尔质量大于或等于8000的PEG不符合排阻体积现象，不能容纳白蛋白。
