Catalyst‐Free One‐Step Preparation of Self‐Crosslinked pH‐Responsive Vesicles

• Published in: Macromolecular rapid communications. 2019-08, Vol.40 (15), p.e1900149-n/a
• Main Authors: Tan, Jidong, Lei, Hengxin, Liaw, Der‐Jang, Chen, Xingxing, Ma, Li, Cui, Chenhui, Zhong, Qianyun, Cheng, Yilong, Zhang, Yanfeng
• Format: Article
• Language: English
• Subjects: Addition polymerization; Alkaline phosphatase; Amines; Block copolymers; Catalysis; Catalysts; Chain transfer; Control stability; Cross-Linking Reagents - chemical synthesis; Cross-Linking Reagents - chemistry; Crosslinking; Dilution; Drug delivery; Drug delivery systems; Dynamic stability; Fabrication; Fluorescein; Fluorescence; hindered urea bond; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; Isocyanates; Light scattering; Membrane permeability; Membrane vesicles; Molecular Structure; Particle Size; pH effects; Photon correlation spectroscopy; pH‐responsive; Polyethylene glycol; Polymerization; Polymers - chemical synthesis; Polymers - chemistry; Reactors; self‐crosslinking; Surface Properties; Urea; Ureas; Vesicles
• ISSN: 1022-1336; 1521-3927
• DOI: 10.1002/marc.201900149

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. The preparation of self‐crosslinked and pH‐responsive vesicles in one step without catalyst is reported here. The hindered urea bonds–included copolymers self‐assemble into membrane‐crosslinked vesicles mediated by isocyanate–amine chemistry in situ through the hydrolysis of the hindered urea bond, and the formed vesicles show promising stability with the dilution of organic solvent and water as well as pH‐controlled size changing.