A new class of biochemically degradable, stimulus-responsive triblock copolymer gelators
A new class of biochemically degradable, stimulus-responsive triblock copolymer gelators
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DOI：
10.1002/anie.200600324
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Lewis, Andrew L.
中科院分区：
文献类型：
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作者：
Li, Chengming;Madsen, Jeppe;Lewis, Andrew L.
人们对生物相容性水凝胶在各种生物医学上的应用越来越感兴趣刺激反应性水凝胶是特别令人感兴趣的，因为在复杂腔内原位形成空间填充凝胶对于某些应用（例如伤口敷料）很重要生物化学反应性水凝胶也受到越来越多的关注。例如，Miyata等人报道了一类新的水凝胶，通过特异性抗原-抗体相互作用交联，对溶液中过量的抗原反应膨胀类似地，普伦基特等。最近证明，用四肽交联剂制备的聚丙烯酰胺水凝胶在α-凝乳胰蛋白酶存在下可降解。[4a]其他一些酶反应性水凝胶的例子也被报道过。[4b， c]然而，我们还没有发现任何关于水凝胶既具有生物化学反应（降解）又具有刺激反应（凝胶化）的报道。二硫化物-硫醇化学为蛋白质化学家所熟知，在常规聚合物合成中越来越受欢迎。最近的论文描述了使用基于二硫化物的二乙烯基单体和引发剂来制备可降解凝胶、水凝胶、微凝胶和支链共聚物这种方法的一个优点是，在温和的条件下，二硫键可以使用试剂，如二硫苏糖醇（DTT）最近，我们报道了用原子转移自由基聚合[8]（ATRP）合成新的生物相容性、热响应性的ABA三嵌段共聚物[7]。采用双功能中位2,5 -二溴己二酸二乙酯（DEDBA）引发剂，先聚合2-（甲基丙烯酰氧基）乙基磷胆碱（MPC），再聚合n -异丙基丙烯酰胺（NIPAM）。在本研究中，我们用先前由Tsarevsky和Matyjaszewski报道的基于二硫化物的引发剂（双[2-（2-溴异丁基氧基）乙基]二硫化物或（BiBOE） 2S2）取代了DEDBA（图1）。PNIPAM80-PMPC125-SS-PMPC125-PNIPAM80三嵌段共聚物的合成使用了与先前描述的DEDBA引发剂基本相同的ATRP协议（见支持信息）自嵌段实验证实了Br-PMPCm-SS-PMPCm-Br宏观引发剂的效率较高，因此三嵌段共聚物的体系结构有望得到很好的确定。凝胶渗透色谱法（GPC）在408C三氯甲烷/甲醇混合洗脱液中的研究
There is increasing interest in biocompatible hydrogels for various biomedical applications.[1] Stimulus-responsive hydrogels are of particular interest as the formation of space-filling gels within complex cavities in situ is important for certain applications, for example, wound dressings.[2] Increasing attention is also being paid to biochemically responsive hydrogels. For example, Miyata et al. reported a new class of hydrogels, cross-linked by a specific antigen–antibody interaction, that swell in response to excess antigen in solution.[3] Similarly, Plunkett etal. recently demonstrated that polyacrylamide hydrogels prepared by using a tetrapeptide crosslinker are degraded in the presence of α-chymotrypsin.[4a] A number of other examples of enzyme-responsive hydrogels have also been reported.[4b, c] However, we are not aware of any reports of hydrogels that are both biochemically responsive (with respect to degradation) and stimulus responsive (with respect to gelation). Disulfide–thiol chemistry is well known to protein chemists and is becoming increasingly popular in conventional polymer syntheses. Recent papers describe the use of disulfide-based divinyl monomers and initiators to prepare degradable gels, hydrogels, microgels, and branched copolymers.[5] One advantage of this approach is that the disulfide bond can be cleaved specifically under mild conditions by using reagents such as dithiothreitol (DTT).[6] Recently, we reported the synthesis of new biocompatible, thermo-responsive ABA triblock copolymer gelators [7] by atom transfer radical polymerization [8](ATRP). A bifunctional diethyl-meso-2, 5-dibromoadipate (DEDBA) initiator was used to polymerize first 2-(methacryloyloxy) ethyl phosphorylcholine (MPC) followed by N-isopropylacrylamide (NIPAM). In the present study we replaced DEDBA with the disulfide-based initiator (bis [2-(2-bromoisobutyryloxy) ethyl] disulfide or (BiBOE) 2S2), which was previously reported by Tsarevsky and Matyjaszewski (Figure 1).[9]The PNIPAM80–PMPC125-SS-PMPC125–PNIPAM80 triblock copolymer was synthesized by using essentially the same ATRP protocol as that previously described for the DEDBA initiator (see the Supporting Information).[7] Selfblocking experiments confirmed that the efficiency of the Br–PMPCm-SS-PMPCm–Br macro-initiator was high, hence the triblock copolymer architecture was expected to be well defined. Gel permeation chromatography (GPC) studies in a 3: 1 chloroform/methanol mixed eluent at 408C with a series