The development of effective approaches to synthesize smart amphiphilic block copolymers (ABPs) exhibiting acid‐responsive degradation through the cleavage of acid‐labile imine bonds is extensively explored for controlled release of encapsulated biomolecules, particularly in drug delivery. Here, a new approach based on direct polymerization utilizing a controlled radical polymerization technique to synthesize acid‐degradable ABPs bearing pendant imine linkages in hydrophobic block is reported. The approach centers on the synthesis of a novel methacrylate bearing benzoic imine group that can be polymerized to form the hydrophobic imine pendant block. The formed ABPs respond to mild acidic pHs equivalent to tumoral and endosomal/lysosomal acidic environments. This causes the dissociation of self‐assembled nanoassemblies through change in their hydrophilic/hydrophobic balance upon the cleavage of pendant imine linkages to the corresponding aldehyde and primary amine, thus leading to the enhanced release of encapsulated drugs. The proof‐of‐concept results suggest that this robust approach is versatile to further design advanced nanoassemblies responding to dual/multiple stimuli, thus being more effective to intracellular drug delivery.

中文翻译：

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直接聚合方法可合成带有亚胺吊坠的可酸降解的嵌段共聚物，以调节pH值并增强释放。

广泛探索了开发有效的两亲嵌段共聚物（ABP）的方法，该方法通过酸不稳定的亚胺键的裂解表现出对酸的响应降解，从而可以控制释放包封的生物分子，特别是在药物递送中。在这里，报道了一种基于直接聚合的新方法，该方法利用可控的自由基聚合技术来合成在疏水嵌段中带有亚胺侧链的酸可降解ABP。该方法集中于合成带有苯甲亚胺基团的新型甲基丙烯酸酯，该甲基丙烯酸酯可聚合形成疏水亚胺侧链嵌段。形成的ABP对相当于肿瘤和内体/溶酶体酸性环境的弱酸性pH作出反应。这会通过亚胺侧链与相应的醛和伯胺的裂解而改变亲水/疏水平衡，从而导致自组装纳米组装体解离，从而提高了封装药物的释放。概念验证的结果表明，这种可靠的方法可用于进一步设计对双重/多重刺激作出响应的高级纳米组件，从而对细胞内药物传递更加有效。