Xanthate-based copolymerisations of 2-methylene-1,3-dioxepane (MDO) and vinyl acetate-derivative monomers were conducted using a versatile mPEG macroCTA to create degradable amphiphilic block copolymers that can undergo self-assembly and crosslinking reactions. Two different block copolymer systems were synthesised; one from vinyl bromobutanoate (VBr) that, after modification, would exhibit permanent crosslinking, and the other from vinyl levulinate (VL) that would have labile crosslinks under acidic pH. The copolymerisations of VBr exhibited excellent control over molecular weight, monomer incorporation and end-group retention, and were able to undergo nucleophilic substitution of the bromo-side chains to form azide-functional copolymers. Conversely, the VL copolymers tended to show less control over molecular weight and end group retention. However, both sets of copolymers were able to undergo self-assembly and with subsequent crosslinking under controlled conditions into micellar nanoparticles via strain promoted azide–alkyne cycloaddition (SPAAC) or hydrazone formation for the azide and ketone functional copolymers, respectively. These nanoparticle systems showed differing stabilities under hydrolytic degradation conditions though they contained a similar amount of degradable ester units in the polymer backbone. Depending on the crosslinking density, the reversible hydrazone linkages destabilized within a few days under physiological conditions (PBS, pH 7.4, 37 °C) as opposed to the stable SPAAC linkages which were intact over many days. Moreover, these materials resembling clinically relevant polycaprolactone (PCL) showed insignificant cytotoxicity towards mouse NIH-3T3 fibroblast and RAW264.7 macrophage cell lines, and displayed unique cellular drug delivery behaviour depending on the crosslinking system.

中文翻译：

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可生物降解的 mPEG-b-聚（MDO-共聚乙烯基酯）嵌段共聚物作为可行的纳米载体平台，具有可调节的分解能力

使用通用的 mPEG MacroCTA 进行 2-亚甲基-1,3-二氧杂环己烷 (MDO) 和乙酸乙烯酯衍生物单体的黄原酸酯共聚，以产生可进行自组装和交联反应的可降解两亲性嵌段共聚物。合成了两种不同的嵌段共聚物体系；一种来自溴丁酸乙烯酯 (VBr)，改性后会表现出永久交联，另一种来自乙酰丙酸乙烯酯 (VL)，在酸性 pH 下会产生不稳定的交联。VBr 的共聚对分子量、单体掺入和端基保留表现出优异的控制，并且能够对溴侧链进行亲核取代，形成叠氮官能共聚物。相反，VL 共聚物对分子量和端基保留的控制往往较差。然而，两组共聚物都能够进行自组装，并随后在受控条件下通过应变促进叠氮化物-炔环加成（SPAAC）或叠氮化物和酮功能共聚物分别形成腙，交联成胶束纳米颗粒。这些纳米粒子系统在水解降解条件下表现出不同的稳定性，尽管它们在聚合物主链中含有相似数量的可降解酯单元。根据交联密度，可逆腙键在生理条件（PBS，pH 7.4，37°C）下几天内就会不稳定，而稳定的 SPAAC 键则在许多天内保持完整。此外，这些类似于临床相关聚己内酯（PCL）的材料对小鼠NIH-3T3成纤维细胞和RAW264.7巨噬细胞系表现出微弱的细胞毒性，并根据交联系统表现出独特的细胞药物递送行为。