Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2‐hydroxyethyl methacrylate‐g‐poly(N‐isopropylacrylamide‐st‐N‐hydroxyethylacrylamide)) (cb‐P(HEMA‐g‐P(NIPAAm‐st‐HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm‐st‐HEAAm), is designed and synthesized successfully via a graft‐from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia‐triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia‐induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug‐loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.

中文翻译：

---

具有增强治疗功效的抗癌药物传递热敏性环状刷式共聚物的制备

环状刷式聚合物在药物递送应用中的适应性在很大程度上仍未开发。在此，聚环状刷共聚物（2-羟乙基丙烯酸甲酯-克-聚（Ñ -isopropylacrylamide- ST-N -hydroxyethylacrylamide））（CB -P（HEMA-克-P（NIPAAm- ST -HEAAm））），其包括PHEMA和P的统计共聚物的热敏刷子（NIPAAm-的环核ST-HEAAm）是通过使用环状多分子引发剂的原子转移自由基聚合通过接枝方法成功设计和合成的。优化了刷子的成分，使所得的环状刷子共聚物的临界溶液温度（LCST）略低于生理温度，但低于肿瘤组织的局部温度，因此适用于通过高温触发的抗癌药物递送。关键聚集浓度的测定揭示了由环状刷状共聚物形成的单分子纳米颗粒比由刷状类似物形成的单分子纳米颗粒具有更好的稳定性。LCST的温度从低于温度升高到高于LCST时，尺寸急剧增加，这证实了两种制剂均会因热疗而引起聚集。这种结构不稳定会在40°C时显着促进药物释放。最重要的是，载有药物的环状刷状共聚物比对等的牙刷显示出更高的针对HeLa细胞的体外细胞毒性。较好的稳定性和更高的治疗功效表明，对于控释药物而言，热敏性环状刷状共聚物比瓶刷状共聚物具有更好的配方。