title: Biocompatible, pH-sensitive AB(2) Miktoarm Polymer-Based Polymersomes: Preparation, Characterization, and Acidic pH-Activated Nanostructural Transformation.
abstract: 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.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, The University of Utah, 421 Wakara Way, Suite 318, Salt Lake City, Utah 84108, USA.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Yin
authors.forename: Han Chang
authors.initials: HC
authors.lastname: Kang
authors.forename: Kang Moo
authors.initials: KM
authors.lastname: Huh
authors.forename: You Han
authors.initials: YH
authors.lastname: Bae