Cellular uptake and targeting of low dispersity, dual emissive, segmented block copolymer nanofibers.
Cellular uptake and targeting of low dispersity, dual emissive, segmented block copolymer nanofibers.
复制标题
DOI：
10.1039/d0sc02593c
复制
发表时间：
2020-07-08
期刊：
影响因子：
8.4
通讯作者：
Manners I
中科院分区：
文献类型：
--
作者：
Street STG;He Y;Jin XH;Hodgson L;Verkade P;Manners I
基于聚合物的纳米颗粒在癌症和其他疾病的治疗和诊断中显示出巨大的希望。在这里，我们报告了定制的，低分散性分段的1D纳米粒子的细胞摄取的探索，其制备从两亲性嵌段共聚物，聚（二己基芴）-b-聚（乙二醇）（PDHF 13-b-PEG 227），与结晶PDHF核心形成块和“隐形”PEG冠形成块与不同的端基功能。采用活性结晶驱动自组装（CDSA）种子生长法制备了具有不同空间定义的冠状化学和选定长度（95 nm）的节段C-B-A-B-C五块一维纳米纤维。由于PDHF的蓝色荧光经常受到环境相关的淬灭，因此将远红BODIPY（BD）荧光团连接到冠状B片段的PEG端基以提供额外的跟踪能力。叶酸（FA）也作为靶向基团并入末端C区段中。通过流式细胞术，这些双发射五嵌段纳米纤维表现出摄取到>97%的叶酸受体阳性HeLa细胞中。在不存在FA的情况下，没有检测到显著的摄取，并且具有FA或BD冠状组的纳米纤维没有显示出显著的毒性。相关的光学和电子显微镜（CLEM）的研究表明受体介导的内吞作用作为一种摄取途径，随后定位到核周区域。一个显着的比例的纳米纤维也出现与细胞膜的端上的方式，这是耦合与荧光淬灭的PDHF核心相互作用。这些结果为基于聚合物的纳米纤维的细胞摄取提供了新的见解，并表明它们在靶向治疗和诊断中的潜在用途。已经研究了具有结晶π-共辄核的定制的、模块化的和分段的低分散性纳米纤维的细胞摄取。
Polymer-based nanoparticles show substantial promise in the treatment and diagnosis of cancer and other diseases. Herein we report an exploration of the cellular uptake of tailored, low dispersity segmented 1D nanoparticles which were prepared from an amphiphilic block copolymer, poly(dihexylfluorene)-b-poly(ethyleneglycol) (PDHF13-b-PEG227), with a crystallizable PDHF core-forming block and a ‘stealth’ PEG corona-forming block with different end-group functionalities. Segmented C–B–A–B–C pentablock 1D nanofibers with varied spatially-defined coronal chemistries and a selected length (95 nm) were prepared using the living crystallization-driven self-assembly (CDSA) seeded-growth method. As the blue fluorescence of PDHF is often subject to environment-related quenching, a far-red BODIPY (BD) fluorophore was attached to the PEG end-group of the coronal B segments to provide additional tracking capability. Folic acid (FA) was also incorporated as a targeting group in the terminal C segments. These dual-emissive pentablock nanofibers exhibited uptake into >97% of folate receptor positive HeLa cells by flow cytometry. In the absence of FA, no significant uptake was detected and nanofibers with either FA or BD coronal groups showed no significant toxicity. Correlative light and electron microscopy (CLEM) studies revealed receptor-mediated endocytosis as an uptake pathway, with subsequent localization to the perinuclear region. A significant proportion of the nanofibers also appeared to interact with the cell membrane in an end-on fashion, which was coupled with fluorescence quenching of the PDHF core. These results provide new insights into the cellular uptake of polymer-based nanofibers and suggest their potential use in targeted therapies and diagnostics. The cellular uptake of tailored, modular, and segmented low dispersity nanofibers with a crystalline π-conjugated core has been studied.
登录
查看更多内容
影响因子：
46.2
作者：
Elsabahy M;Wooley KL
通讯作者：
Wooley KL
影响因子：
15
作者：
Arno MC;Inam M;Coe Z;Cambridge G;Macdougall LJ;Keogh R;Dove AP;O'Reilly RK
通讯作者：
O'Reilly RK
影响因子：
8.4
作者：
Fernández M;Javaid F;Chudasama V
通讯作者：
Chudasama V
影响因子：
5.8
作者：
Deng, Kaicheng;Zhao, Xuezhi;Wei, Hua
通讯作者：
Wei, Hua
pH 触发主动靶向聚合物胶束的细胞内释放
影响因子：
14
作者：
Guo, Xing;Shi, Chunli;Zhou, Shaobing
通讯作者：
Zhou, Shaobing