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Fabrication of theranostic amphiphilic conjugated bottlebrush copolymers with alternating heterografts for cell imaging and anticancer drug delivery†
Polymer Chemistry ( IF 4.1 ) Pub Date : 2018-08-27 00:00:00 , DOI: 10.1039/c8py01221k
Fangjun Liu 1, 2, 3, 4, 5 , Xuezhi Zhao 1, 2, 3, 4, 5 , Xiaolong Zhang 1, 2, 3, 4, 5 , Xianshuo Zhang 1, 2, 3, 4, 5 , Jinlei Peng 1, 2, 3, 4, 5 , Huiru Yang 1, 2, 3, 4, 5 , Kaicheng Deng 1, 2, 3, 4, 5 , Liwei Ma 1, 2, 3, 4, 5 , Cong Chang 6, 7, 8, 9, 10 , Hua Wei 1, 2, 3, 4, 5
Affiliation  

Bottlebrush (bb) copolymers with hetero-polymer grafts represent an intriguing advanced macromolecular architecture due to the unique phase-separation of the pendant side chains for polymer self-assembly and various functionalizations. However, compared to the well-developed polyfluorene (PF)-backboned bb copolymers with homobrushes, the incorporation of heterobrushes remains unexplored likely due to the synthetic challenges. For this purpose, we reported in this study the synthesis of a series of well-defined amphiphilic conjugated bb copolymers, PF-((g-PCL-OOCCH3)-alt-(g-POEGMA)) with alternating poly(oligo(ethylene glycol)monomethyl ether methacrylate) (POEGMA)/poly(ε-caprolactone) (PCL) grafts, by integrated state-of-the-art polymer chemistry techniques including Suzuki-coupling polycondensation, ring-opening polymerization (ROP), click reaction and atom transfer radical polymerization (ATRP). One identified polymer construct (P4) was able to form stabilized unimolecular micelles in an aqueous solution with a diameter of approximately 68 nm and showed the highest fluorescence quantum yield of 0.55, which is on a par with that of the small organic molecular fluorophore standard, quinine sulfate. The potential of P4 for simultaneous cell imaging and drug delivery was further evaluated in vitro, which confirmed efficient cellular uptake and cytotoxicity in HeLa cells. This study thus presents the first example of PF-backboned bb copolymers with alternating heterobrushes for cancer theranostics.

中文翻译:

制备具有交替异质移植物的治疗性两亲性共轭瓶刷共聚物,以进行细胞成像和抗癌药物递送

带有杂聚物接枝的洗瓶刷(bb)共聚物代表了一种引人入胜的先进大分子结构,这是由于侧链侧链的独特相分离可实现聚合物的自组装和各种功能化。但是,与发达的带有均刷的聚芴(PF)交联的bb共聚物相比,由于合成方面的挑战,杂化刷的掺入仍未探索。为了这个目的,我们在本研究中报道了一系列的合成良好定义的两亲性共轭BB共聚物,PF - ((-PCL-OOCCH 3) - ALT - (-POEGMA))与包括聚(Suzuki-coupling缩聚)在内的最先进的聚合物化学技术交替使用交替的聚(低聚(乙二醇)单甲醚甲基丙烯酸甲酯(POEGMA)/聚(ε-己内酯)(PCL)接枝)开环聚合(ROP),点击反应和原子转移自由基聚合(ATRP)。一种确定的聚合物构建体(P 4)能够在直径约为68 nm的水溶液中形成稳定的单分子胶束,并显示出最高的0.55荧光量子产率,与小有机分子荧光团标准品相当硫酸奎宁。在体外进一步评估了P 4同时进行细胞成像和药物递送的潜力,这证实了HeLa细胞中有效的细胞摄取和细胞毒性。因此,本研究提供了用于癌症治疗的PF交联的bb共聚物与交替的异质刷的第一个实例。
更新日期:2018-08-27
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