Amphiphilic TEMPO-Functionalized Block Copolymers: Synthesis, Self-Assembly and Redox-Responsive Disassembly Behavior, and Potential Application in Triggered Drug Delivery
作者：Shen, Xianbo; Cao, Shixiong; Zhang, Qi; Zhang, Jinchao; Wang, Jianli*; Ye, Zhibin*
關鍵字：amphiphilic copolymers, redox-responsive behavior,TEMPO, nanovessels, triggered drug delivery
論文來源：期刊
具體來源：ACS Applied Polymer Materials
發表時間：2019年
在這項工作中，我們通過可逆加成-斷裂鏈轉移（RAFT）聚合，隨后進行官能轉化，合成了一系列新型兩親氧化還原響應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出獨特的還原反應性拆解，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觸發的R6G染料作為模型負載從RNPs中釋放。同時，使用CCK-8測定的細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藥物遞送中的潛在應用。
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