Catalyst-Free One-Step Preparation of Self-Crosslinked pH-Responsive Vesicles
Catalyst-Free One-Step Preparation of Self-Crosslinked pH-Responsive Vesicles
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无催化剂一步制备自交联 pH 响应囊泡。
DOI：
10.1002/marc.201900149
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发表时间：
2019
影响因子：
4.6
通讯作者：
Zhang Yanfeng
中科院分区：
文献类型：
--
作者：
Tan Jidong;Lei Hengxin;Liaw Der jang;Chen Xingxing;Ma L;Cui Chenhui;Zhong Qianyun;Cheng Yilong;Zhang Yanfeng
制备具有可控膜渗透性和良好稳定性的嵌段共聚物（BCP）囊泡仍然是一个相当大的挑战。本文报道了一种基于水解受阻脲键的新型pH响应性自交联囊泡。这种囊泡是由pH响应性和水解自交联共聚物聚（乙二醇）-嵌段-聚[甲基丙烯酸2-（3-（叔丁基）-3-乙基脲基）乙酯-共-甲基丙烯酸2-（二乙氨基）乙酯]（PEG-B-P（TBEU-co-DEA））自组装形成的。BCP可以通过使用基于PEG的大分子链转移剂的甲基丙烯酸2-（3-（叔丁基）-3-乙基脲基）乙酯（TBEU）和甲基丙烯酸2-（二乙基氨基）乙酯（DEA）的可逆加成-断裂链转移（RAFT）聚合容易地合成。在无催化剂的条件下，通过胺与异氰酸酯之间的疏水相互作用和原位交联作用，使受阻脲键水解，使共聚物自组装成稳定的囊泡。动态光散射（DLS）研究表明，囊泡对有机溶剂的稀释表现出增强的稳定性，并且可以通过改变pH值来调节大小。此外，负载碱性磷酸酶的囊泡可以充当纳米反应器，并使小分子自由扩散到囊泡中，随后显著提高磷酸盐笼状荧光素的荧光强度。这种自交联和pH敏感的囊泡可以作为一个智能平台，在控制药物输送和分子反应器。
The fabrication of block copolymer (BCP) vesicles with controlled membrane permeability and promising stability remains a considerable challenge. Herein, a new type of pH‐responsive and self‐crosslinked vesicle based on a hydrolytically hindered urea bond is reported. This kind of vesicle is formed by the self‐assembly of a pH‐responsive and hydrolytically self‐crosslinkable copolymer poly(ethylene glycol)‐block‐poly[2‐(3‐(tert‐butyl)‐3‐ethylureido)ethyl methacrylate‐co‐2‐(diethylamino)ethyl methacrylate] (PEG‐b‐P(TBEU‐co‐DEA)). The BCP can be easily synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization of 2‐(3‐(tert‐butyl)‐3‐ethylureido)ethyl methacrylate (TBEU) and 2‐(diethylamino)ethyl methacrylate (DEA) using PEG‐based macro‐chain transfer agent. The copolymer could self‐assemble into stable vesicles by the hydrophobic interaction and in situ cross‐linking between amines and isocyanates after the hydrolysis of the hindered urea bonds without any catalyst. Dynamic light scattering (DLS) studies show that the vesicles exhibit enhanced stability against the dilution of organic solvent, and the size can be adjusted through the change of pH values. Moreover, the alkaline phosphatase‐loaded vesicles can act as nano‐reactor and enable free diffusion of small molecules into the vesicles, followed by the significantly improved fluorescence intensity of phosphate‐caged fluorescein. This self‐crosslinking and pH‐sensitive vesicles may serve as a smart platform in controlled drug delivery and molecular reactor.