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聚恶唑啉短链的隐形效应:主链末端基团的微小变化决定肝实质细胞类型的特异性。

Stealth Effect of Short Polyoxazolines in Graft Copolymers: Minor Changes of Backbone End Group Determine Liver Cell-Type Specificity.

机构信息

Laboratory of Organic and Macromolecular Chemistry (IOMC), Friedrich Schiller University Jena, Humboldtstraße 10, 07743 Jena, Germany.

Jena Center for Soft Matter (JCSM), Friedrich Schiller University Jena, Philosophenweg 7, 07743 Jena, Germany.

出版信息

ACS Nano. 2021 Jul 27;15(7):12298-12313. doi: 10.1021/acsnano.1c04213. Epub 2021 Jul 16.

DOI:10.1021/acsnano.1c04213
PMID:34270899
Abstract

Dye-loaded micelles of 10 nm diameter formed from amphiphilic graft copolymers composed of a hydrophobic poly(methyl methacrylate) backbone and hydrophilic poly(2-ethyl-2-oxazoline) side chains with a degree of polymerization of 15 were investigated concerning their cellular interaction and uptake as well as their interaction with local and circulating cells of the reticuloendothelial system in the liver by intravital microscopy. Despite the high molar mass of the individual macromolecules ( ≈ 20 kg mol), backbone end group modification by attachment of a hydrophilic anionic fluorescent probe strongly affected the performance. To understand these effects, the end group was additionally modified by the attachment of four methacrylic acid repeating units. Although various micelles appeared similar in dynamic light scattering and cryo-transmission electron microscopy, changes in the micelles were evident from principal component analysis of the Raman spectra. Whereas an efficient stealth effect was found for micelles formed from polymers with anionically charged or thiol end groups, a hydrophobic end group altered the micelles' structure sufficiently to adapt cell-type specificity and stealth properties in the liver.

摘要

直径为 10nm 的染料负载胶束由两亲性接枝共聚物组成,共聚物由疏水性聚(甲基丙烯酸甲酯)主链和亲水性聚(2-乙基-2-恶唑啉)侧链组成,接枝共聚物的聚合度为 15。研究了其细胞相互作用和摄取以及它们与肝脏网状内皮系统的局部和循环细胞的相互作用,采用活体显微镜进行研究。尽管各个大分子的摩尔质量很高(约 20kg/mol),但通过连接亲水性阴离子荧光探针对主链端基进行修饰强烈影响了性能。为了理解这些影响,还通过连接四个甲基丙烯酸重复单元对端基进行了修饰。尽管在动态光散射和冷冻传输电子显微镜中各种胶束看起来相似,但从拉曼光谱的主成分分析可以明显看出胶束的变化。虽然对于带有阴离子或巯基端基的聚合物形成的胶束具有有效的隐身效果,但疏水性端基足以改变胶束的结构,以适应肝脏中的细胞类型特异性和隐身特性。

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