作者：Shen, Xianbo; Cao, Shixiong; Zhang, Qi; Zhang, Jinchao; Wang, Jianli*; Ye, Zhibin*
关键字：amphiphilic copolymers, redox-responsive behavior,TEMPO, nanovessels, triggered drug delivery
论文来源：期刊
具体来源：ACS Applied Polymer Materials
发表时间：2019年

在这项工作中，我们通过可逆加成-断裂链转移（RAFT）聚合，随后进行官能转化，合成了一系列新型两亲氧化还原响应2,2,6,6-四甲基哌啶氧化物（TEMPO）官能化二嵌段共聚物，即聚(乙二醇)-b-聚(2,2,6,6-四甲基哌啶-1-甲基丙烯酸氧基-4-基-co-N-异丙基丙烯酰胺)[PEG-b-P(TMA-co-NIPAM)]，这些亲水性PEG嵌段和含疏水性TEMPO的两亲性二嵌段聚合物可以方便地自组装形成稳定的均匀尺寸的含有基团的纳米颗粒（RNP)，因此可以作为纳米容器携带药物。更有趣的是，自身组装的RNP在添加维生素C（VC）作为代表性还原剂时表现出独特的还原反应性拆解，因为TEMPO单元还原后表面疏水性急剧下降。在概念验证实验中，以可控速率成功地演示了由VC触发的R6G染料作为模型负载从RNPs中释放。同时，使用CCK-8测定的细胞毒性研究证实含有TEMPO的嵌段共聚物和它们的还原物在高达500 μg/ mL的浓度下是无毒的。因此，该系列两亲性二嵌段共聚物非常有希望用于触发药物递送中的潜在应用。

A novel range of amphiphilic redox-responsive 2,2,6,6-tetramethyl-piperidine-1-oxyl (TEMPO)-functionalized diblock copolymers poly-(ethylene glycol)-b-poly-(2,2,6,6-tetramethyl-piperidine-1-oxyl-4-yl methacrylate-co-N-isopropyl-acrylamide [PEG-b-P-(TMA-co-NIPAM)] have been synthesized in this work via reversible addition–fragmentation chain transfer (RAFT polymerization followed with functionality transformation. With the possession of the hydrophilic PEG block and the hydrophobic TEMPO-containing block, these amphiphilic diblock polymers can conveniently self-assemble to form stable uniformly sized radical-containing nanoparticles (RNPs), which can thus act as nanovessels to carry drugs. More interestingly, the self-assembled RNPs exhibit the unique reduction-responsive disassembly upon addition of vitamin C (VC) as a representative reducing agent due to the drastic drop in the surface hydrophobicity following reduction of the TEMPO units. In the proof-of-concept experiments, the VC-triggered release of the encapsulated R6G dye as the model payload from the RNPs at controllable rates has been successfully demonstrated. Meanwhile, the cytotoxicity study with CCK-8 assay confirms the TEMPO-containing block copolymers and their reduced ones are nontoxic at a concentration up to 500 μg mL^–1. This series of amphiphilic diblock copolymers is thus highly promising for potential application in triggered drug delivery. 

DOI: https://doi.org/10.1021/acsapm.9b00293