Polymer micelles with a tunable drug release would be suitable for the concept of drug delivery system. We constructed photo-responsive polymer micelles from amphiphilic block copolymers. The polymer micelles were synthesized by mechanochemical solid-state copolymerization of poly[N-(2-hydroxypropyl)methacrylamide] (PHPMA) and 4,5-dimethoxy-2-nitrobenzyl methacrylate as a photosensitive moiety. The above mechanochemical solid-state copolymerization was performed by vibratory-ball milling at 30 Hz in a nitrogen atmosphere with the use of an agate vessel and an agate ball to yield amphiphilic block copolymers (PHPMA-b-PDNMA). Spherical polymer micelles were formed by the self-assembly of PHPMA-b-PDNMA. The diameter of the PHPMA-b-PDNMA micelles was in the range of 130-200 nm. The PHPMA-b-PDNMA micelles loaded with the antitumor drug 5-fluorouracil (5-FU) showed photo irradiation induced time-dependent release of 5-FU with an associated decrease of micellar size. The drug release profile of the PHPMA-b-PDNMA micelles followed a clear sigmoid curve. Our approach provides a controlled drug release system through the use of photo-responsive polymer micelles, accompanied by the gradual decrease of micellar size. Polymer micelles with a tunable drug release are promising carriers for drug delivery system. It is very important to clarify the correlation between micellar dissociation kinetics and drug release profile on a stimuli-induced deformation of polymer micelles. In this study, photo-cleavable o-nitrobenzyl ester-based amphiphilic block copolymer was successfully designed and prepared by mechanochemical solid-state copolymerization without any solvents and initiators. The self-assembled block copolymer micelles containing anticancer drugs showed sigmoidal decrease of micellar size and released the corresponding drugs depending on the photo-irradiation time.

中文翻译：

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机械化学固相共聚法合成邻硝基苄酯基两亲嵌段共聚物的光响应聚合物胶束

具有可调药物释放的聚合物胶束将适用于药物递送系统的概念。我们从两亲性嵌段共聚物构建了光响应聚合物胶束。聚合物胶束是通过聚[N-（2-羟丙基）甲基丙烯酰胺]（PHPMA）和甲基丙烯酸4,5-二甲氧基-2-硝基苄酯作为光敏部分的机械化学固态共聚反应合成的。通过使用玛瑙容器和玛瑙球在氮气气氛中以 30 Hz 的振动球磨进行上述机械化学固态共聚，以产生两亲性嵌段共聚物 (PHPMA-b-PDNMA)。PHPMA-b-PDNMA自组装形成球形聚合物胶束。PHPMA-b-PDNMA 胶束的直径在 130-200 nm 范围内。装载有抗肿瘤药物 5-氟尿嘧啶 (5-FU) 的 PHPMA-b-PDNMA 胶束显示光照射诱导 5-FU 的时间依赖性释放，并伴随胶束尺寸的减小。PHPMA-b-PDNMA 胶束的药物释放曲线遵循清晰的 sigmoid 曲线。我们的方法通过使用光响应聚合物胶束提供受控的药物释放系统，伴随着胶束尺寸的逐渐减小。具有可调药物释放的聚合物胶束是药物递送系统的有前途的载体。阐明胶束解离动力学与聚合物胶束刺激诱导变形的药物释放曲线之间的相关性非常重要。在这项研究中，光可裂解邻硝基苄酯基两亲嵌段共聚物的设计和制备是通过机械化学固态共聚，无需任何溶剂和引发剂。含有抗癌药物的自组装嵌段共聚物胶束显示胶束尺寸呈 S 型减小，并根据光照射时间释放相应的药物。