Photo/pH dual‐responsive amphiphilic diblock copolymers with alkyne functionalized pendant o‐nitrobenzyl ester group are synthesized using poly(ethylene glycol) as a macroinitiator. The pendant alkynes are functionalized as aldehyde groups by the azide‐alkyne Huisgen cycloaddition. The anticancer drug doxorubicin (DOX) molecules are then covalently conjugated through acid‐sensitive Schiff‐base linkage. The resultant prodrug copolymers self‐assemble into nanomicelles in aqueous solution. The prodrug nanomicelles have a well‐defined morphology with an average size of 20–40 nm. The dual‐stimuli are applied individually or simultaneously to study the release behavior of DOX. Under UV light irradiation, nanomicelles are disassembled due to the ONB ester photocleavage. The light‐controlled DOX release behavior is demonstrated using fluorescence spectroscopy. Due to the pH‐sensitive imine linkage the DOX molecules are released rapidly from the nanomicelles at the acidic pH of 5.0, whereas only minimal amount of DOX molecules is released at the pH of 7.4. The DOX release rate is tunable by applying the dual‐stimuli simultaneously. In vitro studies against colon cancer cells demonstrate that the nanomicelles show the efficient cellular uptake and the intracellular DOX release, indicating that the newly designed copolymers with dual‐stimuli‐response have significant potential applications as a smart nanomedicine against cancer.

中文翻译：

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光和pH响应的聚碳酸酯嵌段共聚物前体药物可控制阿霉素的释放。

具有炔烃官能化侧基o-的光/ pH双响应两亲性两嵌段共聚物使用聚乙二醇作为大分子引发剂合成硝基苄基酯基。叠氮炔-Huisgen环加成将炔烃侧基作为醛基官能化。然后通过酸敏感性席夫碱键将抗癌药阿霉素（DOX）分子共价结合。所得的前药共聚物在水溶液中自组装成纳米胶束。前药纳米胶束具有明确定义的形态，平均大小为20–40 nm。双重刺激可单独或同时应用以研究DOX的释放行为。在紫外光照射下，由于ONB酯的光裂解，纳米胶束被分解。光控制的DOX释放行为已通过荧光光谱进行了证明。由于pH敏感的亚胺键，在酸性pH值为5.0时，DOX分子会从纳米胶束中快速释放出来，而在pH值为7.4时，只有极少量的DOX分子会释放出来。同时应用双重刺激可调节DOX释放速率。针对结肠癌细胞的体外研究表明，纳米胶束显示出有效的细胞摄取和细胞内DOX释放，表明新设计的具有双重刺激反应的共聚物作为针对癌症的智能纳米药物具有重要的潜在应用。