Amphiphilic TEMPO-Functionalized Block Copolymers: Synthesis, Self-Assembly and Redox-Responsive Disassembly Behavior, and Potential Application in Triggered Drug Delivery
writer：Shen, Xianbo; Cao, Shixiong; Zhang, Qi; Zhang, Jinchao; Wang, Jianli*; Ye, Zhibin*
keywords：amphiphilic copolymers, redox-responsive behavior,TEMPO, nanovessels, triggered drug delivery
source：期刊
specific source：ACS Applied Polymer Materials
Issue time：2019年
在這項工作中，我們通過可逆加成-斷裂鏈轉(zhuǎn)移（RAFT）聚合，隨后進行官能轉(zhuǎn)化，合成了一系列新型兩親氧化還原響應(yīng)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-異丙基丙烯酰胺)[PEG-b-P(TMA-co-NIPAM)]，這些親水性PEG嵌段和含疏水性TEMPO的兩親性二嵌段聚合物可以方便地自組裝形成穩(wěn)定的均勻尺寸的含有基團的納米顆粒（RNP)，因此可以作為納米容器攜帶藥物。更有趣的是，自身組裝的RNP在添加維生素C（VC）作為代表性還原劑時表現(xiàn)出獨特的還原反應(yīng)性拆解，因為TEMPO單元還原后表面疏水性急劇下降。在概念驗證實驗中，以可控速率成功地演示了由VC觸發(fā)的R6G染料作為模型負(fù)載從RNPs中釋放。同時，使用CCK-8測定的細(xì)胞毒性研究證實含有TEMPO的嵌段共聚物和它們的還原物在高達(dá)500 μg/ mL的濃度下是無毒的。因此，該系列兩親性二嵌段共聚物非常有希望用于觸發(fā)藥物遞送中的潛在應(yīng)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