Synthetic Bio-nanoreactor: Mechanical and Chemical Control of Polymersome Membrane Permeability
Synthetic Bio-nanoreactor: Mechanical and Chemical Control of Polymersome Membrane Permeability
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DOI：
10.1002/anie.201108814
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发表时间：
2012-01-01
影响因子：
16.6
通讯作者：
Voit, Brigitte
中科院分区：
文献类型：
--
作者：
Gaitzsch, Jens;Appelhans, Dietmar;Voit, Brigitte
在过去的十年里，化学和生物学的结合引起了科学家们越来越多的兴趣。化学家的目标已成为通过化学手段模仿生物结构。[1]这方面的一个很好的例子是开发完全合成的脂质囊泡类似物。这些被认为是生命进化的关键组成部分，因为它们将允许复杂的生化过程发生必要的划分。[1，2]在过去的几年里，特别是，基于聚合物的等价物，聚合物囊泡，已被发现是一个有前途的候选人。[3-6]一些报道表明，聚合物囊泡可用于包裹DNA，[7] RNA，[8，9]以及功能性酶。[4，5，10-14]与脂质体相比，聚合物囊泡的一个很大优势是其更高的机械和化学稳定性。聚合物囊泡的化学设计的高度灵活性允许形成具有可调渗透性的膜。[15-19]这种方法可以通过掺入活性分子转运蛋白如跨膜蛋白来进一步增强。[5，20]然而，尚不确定聚合物囊泡膜是否能够承受高剪切速率，这可能发生在工业清洁过程中。[16]在这里，我们提出了一种新的方法来调制的渗透性的聚合物囊泡膜通过使用pH敏感的光交联共聚物。我们的目的是产生交联聚合物囊泡，以调节不同大小的球状树枝状糖共聚物的剪切速率诱导释放[21]。这个概念然后被进一步扩展到聚合物囊泡内的酶促反应，目的是通过调节pH值来控制跨膜交通。我们的两亲性嵌段共聚物由众所周知的生物相容性和非免疫原性的聚乙二醇（PEG）作为亲水部分组成。疏水部分是pH敏感的甲基丙烯酸二乙基氨基乙酯（DEAEM）和甲基丙烯酸3，4-二甲基马来酰亚胺乙酯（DMIEM，C2聚合物）或甲基丙烯酸3，4-二甲基马来酰亚胺丁酯（DMIBM，C4聚合物）的光交联单元的统计共聚物，分别为10或20mol%（方案1和表1）。我们先前[22]表明，我们的共聚物C2-10和C2-20（方案1）能够形成具有光交叉交联和pH敏感部分的聚合物囊泡。此外，染料分子通过交联聚合物囊泡的跨膜运输可以由pH值的变化触发。[22]然而，80分钟的交联时间[22]可能会破坏最终封闭在其中的生物活性分子的任何功能。我们现在能够减少达到交联所需的UV照射时间，
The combination of chemistry and biology has gained increased interest among scientists over the past decade. The goal of chemists has become to mimic biological structures by chemical means.[1] A good example of this is the development of wholly synthetic analogues of lipid vesicles. These are thought to be critical components in the evolution of life, since they would allow the necessary compartmentalization for complex biochemical processes to take place.[1, 2] Within the last few years, in particular, a polymer-based equivalent, the polymersome, has been found to be a promising candidate for this.[3–6] Several reports have shown that polymersomes can be used to encapsulate DNA,[7] RNA,[8, 9] as well as functional enzymes.[4, 5, 10–14] A great advantage of polymersomes over liposomes is their higher mechanical and chemical stability. The high flexibility in the chemical design of polymersomes allows the formation of membranes with tunable permeability.[15–19] This approach can be further enhanced by the incorporation of active molecular transporters such as transmembrane proteins.[5, 20] However, it is not certain whether polymersome membranes can withstand high shear rates, which may occur during an industrial cleaning process.[16] Here, we present a new approach to modulate the permeability of polymersome membranes by using pH-sensitive photo-cross-linkable copolymers. We aimed to generate cross-linked polymersomes to tune the shear-rate-induced release of globular dendritic glycopolymers [21] of different sizes. The concept was then further expanded to an enzymatic reaction within polymersomes, with the aim of controlling transmembrane traffic by modulating the pH value.Our amphiphilic block copolymer consists of well-known biocompatible and non-immunogenic poly (ethylene glycol)(PEG) as the hydrophilic part. The hydrophobic part is a statistical copolymer of the pH-sensitive diethyl amino ethyl methacrylate (DEAEM) and a photo-cross-linking unit of either 3, 4-dimethyl maleic imidoethyl methacrylate (DMIEM, C2 polymers) or 3, 4-dimethyl maleic imidobutyl methacrylate (DMIBM, C4 polymers) in 10 or 20mol%, respectively (Scheme 1 and Table 1). We showed previously [22] that our copolymers C2-10 and C2-20 (Scheme1) are able to form polymersomes with a photo-cross-linkable and pH-sensitive moiety. Furthermore, the transmembrane traffic of dye molecules through crosslinked polymersomes could be triggered by changes in the pH value.[22] However, the cross-linking time of 80 minutes [22] was likely to destroy any functionality of a bioactive molecule eventually enclosed within. We are now able to reduce the time of the UV irradiation necessary to reach a cross-linked