树枝臂雪花状高分子作为细胞成像和传递的高支化支架《Biomacromolecules》

Dendronized Arm Snowflake Polymer as a Highly Branched Scaffold for Cellular Imaging and Delivery

Yanhong Liu, Silei Bai, Tong Wu, Chun-Chi Chen, Ying Liu, Xiangyu Chao, and Yugang Bai*

State Key Laboratory of Chem-/Bio-Sensing and Chemometrics, School of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China

Biomacromolecules 2021, 22, 9, 3791–3799

Publication Date: August 2, 2021

https://doi.org/10.1021/acs.biomac.1c00631

Abstract

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.

SUBJECTS:

• Dendrons,

• Encapsulation,

• Fluorescence,

• Polymer scaffolds,

• Star polymers

摘要

支链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，这在功能性聚合物支架的合理设计中非常重要。为此目的，树枝状聚合物和超支化聚合物已被广泛研究，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，以便获得球形3D核-壳结构，但要实现对结构、高分子量、结构和结构的精确控制通常具有挑战性，同时具有高分支度（DoB）。在这篇文章中，我们介绍了一组具有功能核和树枝状臂的雪花状星形聚合物，它们确保了高DoB和整体球状构象，从而有助于将功能部分引入到容易实现的支架上，而不需要高代树枝状。使用聚甘油树枝状物（PGD）作为概念证明，我们提出这种树枝状臂雪花聚合物（DASP）结构可以作为高代PGD的更好的替代品。制备了分子量为750、1220、2120和3740 kDa的DASP，在所有情况下产率均大于85%，我们表明，这些DASP具有尼罗河红的高包封效率，因为它们的高DoB和高生物相容性，因为它们在去除缩酮后具有丰富的羟基性质，以及分子量依赖的高细胞渗透性。引入具有合适激发波长的荧光团，如荧光素和1，3-二苯基氨基苯基β-二酮酸二氟硼隆，可将DASP转化为具有超大斯托克斯位移、窄发射带和适用于长期细胞追踪的稳定内体染色荧光团。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，以有效清除细胞内的金黄色葡萄球菌，该葡萄球菌对许多抗生素不敏感，但是耐甲氧西林金黄色葡萄杆菌感染治疗临床成功的关键靶点。32μg/mL氯霉素和450μg/mL DASP对金黄色葡萄球菌的去除率可提高至99.9%以上。