State Key Laboratory of Chem-/Bio-Sensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China.
State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, Hubei 430062, China.
Biomacromolecules. 2021 Sep 13;22(9):3791-3799. doi: 10.1021/acs.biomac.1c00631. Epub 2021 Aug 2.
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 intracellular , which is insensitive toward many antibiotics but is a key target for the clinical success of methicillin-resistant infection treatment. Elimination of could be improved to >99.9% for chloramphenicol at 32 μg/mL with 450 μg/mL DASP.
支化结构的引入是构建具有所需三维（3D）结构的大分子的主要途径，这在功能聚合物支架的合理设计中非常重要。为此，已广泛研究了树枝状大分子和超支化聚合物，但这些结构的适当功能增益通常需要足够大的分子量和高度支化的内部，以便获得球形 3D 核壳结构，但通常难以同时实现对结构、高分子量和高支化度（DoB）的精确控制。在本文中，我们提出了一组具有功能核心和树枝化臂的雪花形星型聚合物，这些聚合物确保了高 DoB 和整体球形构象，从而便于在易于获得的支架上引入功能部分，而无需使用高代树枝状大分子。使用聚甘油树枝状大分子（PGD）作为概念验证，我们提出这种树枝化臂雪花聚合物（DASP）结构可以作为高性能替代物替代高代 PGD。所有情况下，分子量为 750、1220、2120 和 3740 kDa 的 DASP 均以>85%的产率制备，并且我们表明，由于其高 DoB 和由于缩酮去除后羟基丰富而具有高生物相容性，这些 DASP 对尼罗红具有高包封效率，以及与分子量相关的高细胞通透性。引入合适激发波长的荧光团，如荧光素和二氟化硼 1,3-二苯基氨基苯β-二酮酸酯，可能会使 DASP 变成稳定的、内体染色荧光团，具有超宽的斯托克斯位移、狭窄的发射带，并且适合长期细胞追踪。此外，该支架可以包封抗生素分子并将其递送至吞噬溶酶体中，以有效消除对许多抗生素不敏感但对耐甲氧西林金黄色葡萄球菌感染治疗的临床成功是关键目标的 。用 450 μg/mL DASP 处理时，32 μg/mL 氯霉素的消除率可提高到>99.9%。
