Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties,Biomacromolecules

当前位置： X-MOL 学术 › Biomacromolecules › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Synthesis and in Vitro Evaluation of Monodisperse Amino-Functional Polyester Dendrimers with Rapid Degradability and Antibacterial Properties
Biomacromolecules ( IF 5.5 ) Pub Date : 2017-11-22 00:00:00 , DOI: 10.1021/acs.biomac.7b01364
Patrik Stenström ₁ , Erik Hjorth ₂ , Yuning Zhang ₁ , Oliver C. J. Andrén ₁ , Simon Guette-Marquet ₂ , Marianne Schultzberg ₂ , Michael Malkoch ₁

Affiliation

Amine functional polymers, especially cationically charged, are interesting biomacromolecules for several reasons, including easy cell membrane entrance, their ability to escape endosomes through the proton sponge effect, spontaneous complexation and delivery of drugs and siRNA, and simple functionalization in aqueous solutions. Dendrimers, a subclass of precision polymers, are monodisperse and exhibit a large and exact number of peripheral end groups in relation to their size and have shown promise in drug delivery, biomedical imaging and as antiviral agents. In this work, hydroxyl functional dendrimers of generation 1 to 5 based on 2,2-bis(methylol)propionic acid (bis-MPA) were modified to bear 6 to 96 peripheral amino groups through esterification reactions with beta-alanine. All dendrimers were isolated in high yields and with remarkable monodispersity. This was successfully accomplished utilizing the present advantages of fluoride-promoted esterification (FPE) with imidazole-activated monomers. Straightforward postfunctionalization was conducted on a second generation amino-functional dendrimer with tetraethylene glycol through NHS-amidation and carbonyl diimidazole (CDI) activation to full conversion with short reaction times. Fast biodegradation of the dendrimers through loss of peripheral beta-alanine groups was observed and generational- and dose-dependent cytotoxicity was evaluated with a set of cell lines. An increase in neurotoxicity compared to hydroxyl-functional dendrimers was shown in neuronal cells, however, the dendrimers were slightly less neurotoxic than commercially available poly(amidoamine) dendrimers (PAMAMs). Additionally, their effect on bacteria was evaluated and the second generation dendrimer was found unique inhibiting the growth of Escherichia coli at physiological conditions while being nontoxic toward human cells. Finally, these results cement a robust and sustainable synthetic route to amino-functional polyester dendrimers with interesting chemical and biological properties.

中文翻译：

具有快速降解和抗菌性能的单分散氨基官能聚酯树状大分子的合成及体外评价

胺功能聚合物（尤其是带阳离子的功能性聚合物）是令人感兴趣的生物大分子，其原因有很多，包括容易进入细胞膜，它们通过质子海绵效应逃逸内体的能力，药物和siRNA的自发络合和递送以及在水溶液中的简单功能化。树枝状大分子是精密聚合物的一个子类，是单分散的，相对于其尺寸而言，其末端基团的数目大而准确，并且在药物输送，生物医学成像和作为抗病毒剂方面显示出了希望。在这项工作中，通过与β-丙氨酸的酯化反应，将基于2,2-双（羟甲基）丙酸（bis-MPA）的1-5代羟基官能树状聚合物修饰为带有6-96个外围氨基。所有树枝状聚合物均以高收率和明显的单分散性分离。利用氟化物促进的酯化反应（FPE）与咪唑活化的单体的现有优势，成功完成了这一任务。通过NHS酰胺化和羰基二咪唑（CDI）活化，在第二代氨基官能树状聚合物与四甘醇上进行简单的后官能化，使其在短反应时间内完全转化。观察到树状聚合物通过失去外围的β-丙氨酸基团而快速生物降解，并用一组细胞系评估了世代和剂量依赖性的细胞毒性。在神经元细胞中，与羟基官能树状聚合物相比，神经毒性增加了，但是，树枝状聚合物的神经毒性比市售的聚（酰胺基胺）树枝状聚合物（PAMAMs）略低。此外，评估了它们对细菌的作用，发现第二代树状聚合物独特地抑制了细菌的生长。大肠杆菌在生理条件下，对人体细胞无毒。最后，这些结果巩固了具有有趣的化学和生物学特性的氨基官能聚酯树状聚合物的稳健而可持续的合成途径。

更新日期：2017-11-23

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11