Dendronized Arm Snowflake Polymer as a Highly Branched Scaffold for Cellular Imaging and Delivery
Dendronized Arm Snowflake Polymer as a Highly Branched Scaffold for Cellular Imaging and Delivery
复制标题
树枝化臂雪花聚合物作为细胞成像和传递的高度支化支架
DOI：
10.1021/acs.biomac.1c00631
复制
发表时间：
2021-08-02
影响因子：
6.2
通讯作者：
Bai，Yugang
中科院分区：
文献类型：
--
作者：
Liu，Yanhong;Bai，Silei;Bai，Yugang
支链结构的掺入是构建具有理想三维结构的大分子的主要途径，对功能高分子支架的合理设计具有重要意义。树状大分子和超支化聚合物已经为此目的进行了广泛的研究，但是这些结构的适当的功能获得通常需要足够大的分子量和高度分支的内部，以便获得球形的三维核壳结构，然而，同时实现对结构，高分子量和高分支度（DoB）的精确控制通常具有挑战性。在这篇文章中，我们提出了一组雪花形状的星形聚合物，具有功能核心和树突臂，确保了高DoB和整体的球形构象，从而促进了功能部分的引入，而不需要高代树突。使用聚甘油树突（PGD）作为概念证明，我们提出这种树突化臂雪花聚合物（DASP）结构可以作为高代PGD的更好性能替代品。这些dasp的分子量分别为750、1220、2120和3740 kDa，产率均为bb0 ~ 85%。我们发现，这些dasp具有高DoB的尼罗河红包封效率，去除酮后富含羟基的性质具有高生物相容性，以及依赖于分子量的高细胞通透性。在合适的激发波长下引入荧光素和二氟硼1,3-二苯基氨基苯基β-二酮酸等荧光团，可以使dass变成稳定的、具有超大斯托克斯位移、窄发射带、适合长期细胞示迹的内体染色荧光团。此外，该支架可以包裹抗生素分子并将其递送到吞噬溶酶体中，从而有效消除对许多抗生素不敏感的细胞内金黄色葡萄球菌，这是临床成功治疗耐甲氧西林金黄色葡萄球菌感染的关键靶点。当DASP为450 μg/mL时，32 μg/mL的氯霉素对金黄色葡萄球菌的去除率可达99.9%。
Incorporation of branched structures is a major pathway to build macromolecules with desired three-dimensional (3D) structures, which are of high importance in the rational design of functional polymeric scaffolds. Dendrimers and hyperbranched polymers have been extensively studied for this purpose, but proper gain-of-function for these structures usually requires large enough molecular weights and a highly branched interior so that a spherical 3D core–shell architecture can be obtained, yet it is generally challenging to achieve precise control over the structure, high molecular weight, and high degree of branching (DoB) simultaneously. In this article, we present a set of snowflake-shaped star polymers with functional cores and dendronized arms, which ensure a high DoB and an overall globular conformation, thus facilitating the introduction of functional moieties onto the easily achieved scaffold without the need for high-generation dendrons. Using a polyglycerol dendron (PGD) as a proof of concept, we propose that this dendronized arm snowflake polymer (DASP) structure can serve as a better performing alternative to high-generation PGDs. DASPs with molecular weights of 750, 1220, 2120, and 3740 kDa were prepared with >85% yields in all cases, and we show that these DASPs have high encapsulating efficiency of Nile Red due to their high DoB and high biocompatibility due to their hydroxyl-rich nature after ketal removal, as well as high cell permeability that is molecular-weight-dependent. Introduced fluorophores such as fluorescein and difluoroboron 1,3-diphenylaminophenyl β-diketonate with suitable excitation wavelengths may turn the DASPs into stable, endosome-staining fluorophores with ultra-large Stokes shifts, narrowed emission bands, and suitability for long-term cellular tracing. Moreover, the scaffold can encapsulate antibiotic molecules and deliver them into phagolysosomes for efficient elimination of intracellularStaphylococcus aureus, which is insensitive toward many antibiotics but is a key target for the clinical success of methicillin-resistantStaphylococcus aureusinfection treatment. Elimination ofStaphylococcus aureuscould be improved to >99.9% for chloramphenicol at 32 μg/mL with 450 μg/mL DASP.