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 Staphylococcus aureus, which is insensitive toward many antibiotics but is a key target for the clinical success of methicillin-resistant Staphylococcus aureus infection treatment. Elimination of Staphylococcus aureus could be improved to >99.9% for chloramphenicol at 32 μg/mL with 450 μg/mL DASP.

中文翻译：

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树枝化臂雪花聚合物作为用于细胞成像和递送的高度支化支架

支化结构的结合是构建具有所需三维（3D）结构的大分子的主要途径，这对于功能性聚合物支架的合理设计具有重要意义。为此目的，已经对树枝状大分子和超支化聚合物进行了广泛的研究，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，以便可以获得球形 3D 核壳结构，但通常同时实现对结构、高分子量和高支化度 (DoB) 的精确控制具有挑战性。在本文中，我们展示了一组具有功能核心和树枝状臂的雪花形星形聚合物，可确保高 DoB 和整体球状构象，从而促进将功能部分引入到容易获得的支架上，而无需高代树突。使用聚甘油树突 (PGD) 作为概念证明，我们建议这种树枝化的臂雪花聚合物 (DASP) 结构可以作为高性能 PGD 的更好替代品。在所有情况下均以 >85% 的产率制备了分子量为 750、1220、2120 和 3740 kDa 的 DASP，我们表明，这些 DASP 由于其高 DoB 和高生物相容性，因此具有高的尼罗红包封率。去除缩酮后的丰富性质，以及依赖于分子量的高细胞渗透性。引入荧光素和二氟硼1等荧光团，具有合适激发波长的 3-二苯氨基苯基 β-二酮酸酯可以将 DASP 转变为稳定的内体染色荧光团，具有超大的斯托克斯位移、窄发射带和适合长期细胞追踪的特性。此外，支架可以包裹抗生素分子并将其递送到吞噬溶酶体中，以有效消除细胞内金黄色葡萄球菌对许多抗生素不敏感，但它是耐甲氧西林金黄色葡萄球菌感染治疗临床成功的关键目标。对于 32 μg/mL 和 450 μg/mL DASP 的氯霉素，金黄色葡萄球菌的清除率可提高到 >99.9%。