Department of Applied Chemistry, School of Science MOE Key Laboratory for Nonequilibrium Synthesis and Modulation of Condensed Matter, Xi'an Key Laboratory of Sustainable Energy Materials Chemistry, and State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.
Department of Chemical Engineering, National Taiwan University of Science and Technology, Taipei, 10607, Taiwan.
Macromol Rapid Commun. 2019 Aug;40(15):e1900149. doi: 10.1002/marc.201900149. Epub 2019 May 21.
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.
具有可控膜通透性和良好稳定性的嵌段共聚物（BCP）囊泡的制备仍然是一个巨大的挑战。在此，报道了一种新型 pH 响应和自交联的囊泡，基于水解受阻脲键。这种囊泡是由 pH 响应和可水解自交联共聚物聚乙二醇-嵌段-聚[2-（3-（叔丁基）-3-乙基脲基）乙基甲基丙烯酸酯-co-2-（二乙氨基）乙基甲基丙烯酸酯]（PEG-b-P（TBEU-co-DEA））的自组装形成的。BCP 可以通过可逆加成-断裂链转移（RAFT）聚合 2-（3-（叔丁基）-3-乙基脲基）乙基甲基丙烯酸酯（TBEU）和 2-（二乙氨基）乙基甲基丙烯酸酯（DEA）来轻松合成，使用基于 PEG 的大分子链转移剂。共聚物在受阻脲键水解后，通过胺和异氰酸酯之间的疏水相互作用和原位交联，可以自组装成稳定的囊泡，无需任何催化剂。动态光散射（DLS）研究表明，囊泡在有机溶剂稀释时表现出增强的稳定性，并且可以通过改变 pH 值来调整其尺寸。此外，负载碱性磷酸酶的囊泡可以作为纳米反应器，允许小分子自由扩散到囊泡中，随后荧光素被磷酰基封闭的荧光强度显著提高。这种自交联和 pH 敏感的囊泡可以作为控制药物释放和分子反应器的智能平台。
