Biocompatible, pH-sensitive AB2 miktoarm polymer-based polymersomes: preparation, characterization, and acidic pH-activated nanostructural transformation

• Published in: Journal of materials chemistry Vol. 22; no. 36; pp. 19168 - 19178
• Main Authors: Yin, Haiqing, Kang, Han Chang, Huh, Kang Moo, Bae, You Han
• Format: Journal Article
• Language: English
• Published: 28.09.2012
• ISSN: 0959-9428; 1364-5501
• DOI: 10.1039/c2jm33750a

Motivated by the limitations of liposomal drug delivery systems, we designed a novel histidine-based AB 2 -miktoarm polymer (mPEG- b -(polyHis) 2 ) equipped with a phospholipid-mimic structure, low cytotoxicity, and pH-sensitivity. Using “core-first” click chemistry and ring-opening polymerization, mPEG 2kDa - b -(polyHis 29kDa ) 2 was successfully synthesized with a narrow molecular weight distribution (1.14). In borate buffer (pH 9), the miktoarm polymer self-assembled to form a nano-sized polymersome with a hydrodynamic radius of 70.2 nm and a very narrow size polydispersity (0.05). At 4.2 µmol/mg polymer, mPEG 2kDa - b -(polyHis 29kDa ) 2 strongly buffered against acidification in the endolysosomal pH range and exhibited low cytotoxicity on a 5 d exposure. Below pH 7.4 the polymersome transitioned to cylindrical micelles, spherical micelles, and finally unimers as the pH was decreased. The pH-induced structural transition of mPEG 2kDa - b -(polyHis 29kDa ) 2 nanostructures may be caused by the increasing hydrophilic weight fraction of mPEG 2kDa - b -(polyHis 29kDa ) 2 and can help to disrupt the endosomal membrane through proton buffering and membrane fusion of mPEG 2kDa - b -(polyHis 29kDa ) 2 . In addition, a hydrophilic model dye, 5(6)-carboxyfluorescein encapsulated into the aqueous lumen of the polymersome showed a slow, sustained release at pH 7.4 but greatly accelerated release below pH 6.8, indicating a desirable pH sensitivity of the system in the range of endosomal pH. Therefore, this polymersome that is based on a biocompatible histidine-based miktoarm polymer and undergoes acid-induced transformations could serve as a drug delivery vehicle for chemical and biological drugs.