Temperature Driven Self-Assembly of a Zwitterionic Block Copolymer That Exhibits Triple Thermoresponsivity and pH Sensitivity

Abstract

We report a zwitterionic block copolymer composed of N-isopropylacrylamide and N,N-dimethyl-N-(3-(methacrylamido)propyl)ammoniopropanesulfonate monomers which self-assembles into different structures depending on the solution temperature. As the temperature is increased from 20 to 70°C, the solubility of the polymer switches direction from insoluble to soluble to insoluble to soluble. During this process, the polymer self-assembly changes from polymersomes to micelles. These extraordinary transitions are possible because of the hydrophilic−hydrophobic ratio of the polymer blocks and the presence of a carboxyl end group attached to the end of the poly(N-isopropylacrylamide) chain. Additionally, one of these transitions can be controlled by the pH of the solution thanks to the protonation−deprotonation of the carbonyl and the charge neutralization of the ammonium moieties. The present work opens the possibility of designing polymers with temperature driven self-assembly properties that could be used for biomedical applications. ■ INTRODUCTIONWater-soluble polymers that switch hydrophilicity upon temperature variations are a type of thermoresponsive polymer. When the polymer becomes soluble or insoluble by increasing temperature, it is said to show an upper critical solution temperature 1 (UCST) or lower critical solution temperature (LCST), respectively. 2 This responsivity can be exploited in tissue engineering, 3 chromatography for the separation of biomolecules, 4 patterned-switchable surfaces, 5 preparations for cancer therapy, 6−8 optical devices for sensing and biosensing, 9 DNA transfection, 10 and functional hydrogels, 11 among others. Some zwitterionic polymers like poly(sulfobetaines) show UCST behavior in water. These betaines are ionic polymers derived of dimethylaminoalkyl acrylate or acrylamide monomers containing ammonium and sulfonic ions. Their solubility in water is poor, but an increase in temperature and/or the addition of low-molecular-weight salts solubilize the polymer thanks to the disruption of the ionic network. 12 Additional to the thermoresponsivity, poly(sulfobetaines) have the chemical characteristics necessary to prepare nonfouling materials 13 which make them attractive for the preparation of biomaterials. On the other hand, polymers with LCST transitions like poly(N-isopropylacrylamide) or poly(NIPAAm) become more hydrophobic at higher temperatures and therefore insoluble in water. In a dilute aqueous solution, poly(NIPAAm) is in the extended coil state which collapses into a compact globule state and aggregates above 32°C (LCST). 14 This transition temperature can be shifted to human body temperature by copolymerization with hydrophilic monomers, making it suitable for biomedical applications. 15 Copolymers exhibiting both UCST and LCST transition temperatures can be prepared by synthesis of block copolymers, where each block is responsible for one of the transitions. 16−25 This type of polymer offers a hydrophobic and a hydrophilic block which make them susceptible to self-organiz...

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