Functionalized Poly(ethylene glycol) for Preparation of Biologically Relevant Conjugates
Functionalized Poly(ethylene glycol) for Preparation of Biologically Relevant Conjugates
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DOI：
10.1002/chin.199534317
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发表时间：
1995-08
期刊：
影响因子：
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通讯作者：
S. Zalipsky
中科院分区：
文献类型：
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作者：
S. Zalipsky
最好的生物相容性聚合物之一，聚（乙二醇）（PEG），* 1具有一系列有用的特性（1，2）。其中包括在有机和水介质中的广泛溶解度（2，3），缺乏毒性和免疫原性（4），非生物降解性，以及易于从活生物体中排泄（5）。在过去的二十年中，聚乙二醇（PEG）被广泛地用作各种底物的共价修饰剂，产生结合了起始底物和聚合物的某些性质的联合收割机（6）。用PEG修饰的基底包括低分子量化合物、几乎所有种类的生物大分子以及颗粒和人造材料的表面（见表1）。这一领域的绝大多数工作都是由改变感兴趣的底物的一种或多种性质以使其适合（或更适合）特定生物应用的愿望所推动的。这通常包括溶解度性质的改善、分子量的增加或两相系统中基质的分配性质的改变。然而，随着PEG缀合物的武库及其应用的增加，已经变得明显的是，通过用PEG进行共价修饰可以使由各种生物识别机制在体内触发的许多不期望的作用最小化。例如，可以降低蛋白质的免疫原性和抗原性（4，27）。脂质体、纳米颗粒和蛋白质的血液寿命可以显著延长，网状内皮系统（RES）器官、肝脏和脾脏的摄取减少（25）。在PEG接枝表面的情况下，可以减少促凝性、细胞和蛋白质粘附（26）。PEG传递的这些有益特性对于任何需要血液接触的系统都非常重要。特定PEG缀合物的一些性质及其应用已经成为单独综述的主题（4，12，13，15-19，25，26）。
One of the best biocompatible polymers, poly (ethylene glycol)(PEG),* 1 possesses an array of useful properties (1, 2). Among them are a wide range of solubilities in both organic andaqueous media (2, 3), lack of toxicity and immunogenicity (4), nonbiodegradability, and ease of excretion from living organisms (5). During the last two decades poly (ethylene glycol)(PEG) was used exten-sively as a covalent modifier of a variety ofsubstrates, producing conjugates which combine some of the properties of both the starting substrate and the polymer (6). Substrates modified with PEG include low molecular weight compounds, almost every class of biological mac-romolecules as well as particulates, and surfaces of artificial materials (see Table 1). The overwhelming majority of work in this area was prompted by a desire to alter one or more properties of a substrate of interest to makeit suitable (or more suitable) for a particular biological application. This often included improvement of solubility properties, increase of molecular weight, or change of a substrate’s partition properties in two-phase systems. However, as the arsenals of PEG conjugates and their applications have increased it has become apparent that many undesirable effects triggered in vivo by various biological recognition mechanisms can be minimized by covalent modification with PEG. For example, immunogenicity and antigenicity of proteins can be decreased (4, 27). Blood lifetime of liposomes, nano-particles, and proteins can be significantly extended and their uptake by reticuloendothelial system (RES) organs, liver and spleen, diminished (25). Thrombogenicity, cell and protein adherence, can be reduced in the case of PEG-grafted surfaces (26). These beneficial properties conveyed by PEG are of enormous importance for any system requiring blood contact. Some of the properties of specific PEG conjugates and their applications have been the subject of separate reviews (4, 12, 13, 15—19, 25, 26).