Oxidation-responsive micelles by a one-pot polymerization-induced self-assembly approach†,Polymer Chemistry

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Oxidation-responsive micelles by a one-pot polymerization-induced self-assembly approach†
Polymer Chemistry ( IF 4.1 ) Pub Date : 2018-01-03 00:00:00 , DOI: 10.1039/c7py01859b
Fabian H. Sobotta _{1,

2,

3,

4,

5} , Franziska Hausig _{1,

2,

3,

4,

5} , Dominic O. Harz _{1,

2,

3,

4} , Stephanie Hoeppener _{1,

2,

3,

4,

5} , Ulrich S. Schubert _{1,

2,

3,

4,

5} , Johannes C. Brendel _{1,

2,

3,

4,

5}

Affiliation

The increased levels of reactive oxygen species (ROS) such as hydrogen peroxide in inflamed or cancerous tissue represent a promising trigger for the local and selective release of drugs at the affected areas. Despite new developments in the field of oxidation-responsive drug carrier systems, the preparation of the required materials remains in most cases tedious. Here, we present a novel system, which combines the advantages of a one-pot sequential controlled radical polymerization with the direct polymerization-induced self-assembly (PISA) process. By utilizing highly reactive acrylamide monomers, full conversion can be reached while maintaining a high chain end fidelity in RAFT polymerization, which enables the precise preparation of block copolymers or micelles, respectively, without intermediate purification steps. We demonstrate that the cyclic thioether N-acryloyl thiomorpholine is a versatile monomer for PISA resulting in a hydrophobic block, which upon oxidation can be transformed into a highly water-soluble sulfoxide. The micellar structures are tunable in size by the variation of the block length and feature a good sensitivity towards hydrogen peroxide even at low concentrations of 10 mM resulting in their disintegration. In vitro studies prove the uptake of these micelles into cells without signs of toxicity up to 500 μg mL⁻¹. The straightforward preparation, the excellent biocompatibility and the selective disintegration in the presence of biologically relevant levels of hydrogen peroxide are features that certainly make the presented system an attractive new material for oxidation-responsive drug carriers.

中文翻译：

一锅聚合诱导的自组装方法对氧化反应的胶束†

在发炎或癌变的组织中，诸如过氧化氢之类的活性氧（ROS）水平升高，代表着在受影响区域局部和选择性释放药物的有希望的诱因。尽管在氧化反应性药物载体系统领域中有了新的发展，但是在大多数情况下，所需材料的制备仍然很繁琐。在这里，我们提出了一种新颖的系统，该系统将单锅顺序受控自由基聚合的优势与直接聚合诱导的自组装（PISA）工艺相结合。通过利用高反应性的丙烯酰胺单体，可以在保持RAFT聚合反应的高链端保真度的同时实现完全转化，从而无需中间纯化步骤即可分别精确制备嵌段共聚物或胶束。N-丙烯酰基硫代吗啉是PISA的多用途单体，可产生疏水性嵌段，该嵌段在氧化后可转变为高度水溶性的亚砜。胶束结构的大小可通过改变嵌段长度来调节，并且即使在10 mM的低浓度下也能对过氧化氢具有良好的敏感性，从而导致其分解。体外研究证明，这些胶束摄取到细胞中的毒性迹象不超过500μgmL ^-1。在生物学上相关水平的过氧化氢的存在下，直接的制备，优异的生物相容性和选择性崩解的特征无疑使所提出的系统成为用于氧化反应性药物载体的有吸引力的新材料。

更新日期：2018-01-03

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