Miktoarm Star Polymers with Environment‐Selective ROS/GSH Responsive Locations: From Modular Synthesis to Tuned Drug Release through Micellar Partial Corona Shedding and/or Core Disassembly,Macromolecular Bioscience

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Miktoarm Star Polymers with Environment‐Selective ROS/GSH Responsive Locations: From Modular Synthesis to Tuned Drug Release through Micellar Partial Corona Shedding and/or Core Disassembly
Macromolecular Bioscience ( IF 4.4 ) Pub Date : 2020-11-13 , DOI: 10.1002/mabi.202000305
Victor Lotocki ₁ , Hossein Yazdani _{1,

2} , Qiaochu Zhang _{1,

3} , Evan Rizzel Gran ₃ , Anastasiia Nyrko ₁ , Dusica Maysinger ₃ , Ashok Kakkar ₁

Affiliation

Branched architectures with asymmetric polymeric arms provide an advantageous platform for the construction of tailored nanocarriers for therapeutic interventions. Simple and adaptable synthetic methodologies to amphiphilic miktoarm star polymers have been developed in which spatial location of reactive oxygen species (ROS) and glutathione (GSH) responsive entities is articulated to be on the corona shell surface or inside the core. The design of such architectures is facilitated through versatile building blocks and selected combinations of ring‐opening polymerization, Steglich esterification, and alkyne‐azide click reactions. Soft nanoparticles from aqueous self‐assembly of these stimuli responsive miktoarm stars have low critical micelle concentrations and high drug loading efficiencies. Partial corona shedding upon response to ROS is accompanied by an increase in drug release, without significant changes to overall micelle morphology. The location of the GSH responsive unit at the core leads to micelle disassembly and complete drug release. Curcumin loaded soft nanoparticles show higher efficiencies in preventing ROS generation in extracellular and cellular environments, and in ROS scavenging in human glioblastoma cells. The ease in synthetic elaboration and an understanding of structure‐property relationships in stimuli responsive nanoparticles offer a facile venue for well‐controlled drug delivery, based on the extra‐ and intracellular concentrations of ROS and GSH.

中文翻译：

具有环境选择性 ROS/GSH 响应位置的 Miktoarm 星形聚合物：从模块化合成到通过胶束部分电晕脱落和/或核心分解调节药物释放

具有不对称聚合物臂的分支结构为构建用于治疗干预的定制纳米载体提供了有利的平台。已经开发了简单且适应性强的两亲性 miktoarm 星形聚合物的合成方法，其中活性氧 (ROS) 和谷胱甘肽 (GSH) 响应实体的空间位置被铰接在电晕壳表面或核心内部。这种结构的设计是通过通用的构建块和开环聚合、Steglich 酯化和炔-叠氮化物点击反应的选择组合来促进的。来自这些刺激响应型 miktoarm 星的水性自组装的软纳米粒子具有低临界胶束浓度和高载药效率。响应 ROS 时部分电晕脱落伴随着药物释放的增加，而整体胶束形态没有显着变化。GSH 响应单元在核心的位置导致胶束分解和药物完全释放。加载姜黄素的软纳米颗粒在阻止细胞外和细胞环境中 ROS 的生成以及清除人胶质母细胞瘤细胞中的 ROS 方面表现出更高的效率。基于 ROS 和 GSH 的细胞外和细胞内浓度，合成加工的简便性和对刺激响应性纳米粒子结构-性质关系的理解为良好控制的药物递送提供了一个方便的场所。GSH 响应单元位于核心导致胶束分解和药物完全释放。加载姜黄素的软纳米颗粒在阻止细胞外和细胞环境中 ROS 的生成以及清除人胶质母细胞瘤细胞中的 ROS 方面表现出更高的效率。基于 ROS 和 GSH 的细胞外和细胞内浓度，合成加工的简便性和对刺激响应性纳米粒子结构-性质关系的理解为良好控制的药物递送提供了一个方便的场所。GSH 响应单元位于核心导致胶束分解和药物完全释放。加载姜黄素的软纳米颗粒在防止细胞外和细胞环境中 ROS 生成以及在人胶质母细胞瘤细胞中清除 ROS 方面表现出更高的效率。基于 ROS 和 GSH 的细胞外和细胞内浓度，合成加工的简便性和对刺激响应性纳米粒子结构-性质关系的理解为良好控制的药物递送提供了一个方便的场所。

更新日期：2020-11-13

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