TY - JOUR
T1 - Biocompatible, pH-sensitive AB2 miktoarm polymer-based polymersomes
T2 - Preparation, characterization, and acidic pH-activated nanostructural transformation
AU - Yin, Haiqing
AU - Kang, Han Chang
AU - Huh, Kang Moo
AU - Bae, You Han
PY - 2012/9/28
Y1 - 2012/9/28
N2 - Motivated by the limitations of liposomal drug delivery systems, we designed a novel histidine-based AB2-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, mPEG2kDa-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 per mg polymer, mPEG2kDa-b-(polyHis29kDa)2 strongly buffered against acidification in the endolysosomal pH range and exhibited low cytotoxicity on 5 days 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-(polyHis29kDa)2 nanostructures may be caused by the increasing hydrophilic weight fraction of mPEG2kDa-b- (polyHis29kDa)2 and can help to disrupt the endosomal membrane through proton buffering and membrane fusion of mPEG 2kDa-b-(polyHis29kDa)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.
AB - Motivated by the limitations of liposomal drug delivery systems, we designed a novel histidine-based AB2-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, mPEG2kDa-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 per mg polymer, mPEG2kDa-b-(polyHis29kDa)2 strongly buffered against acidification in the endolysosomal pH range and exhibited low cytotoxicity on 5 days 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-(polyHis29kDa)2 nanostructures may be caused by the increasing hydrophilic weight fraction of mPEG2kDa-b- (polyHis29kDa)2 and can help to disrupt the endosomal membrane through proton buffering and membrane fusion of mPEG 2kDa-b-(polyHis29kDa)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.
UR - https://www.scopus.com/pages/publications/84865217216
U2 - 10.1039/c2jm33750a
DO - 10.1039/c2jm33750a
M3 - Article
AN - SCOPUS:84865217216
SN - 0959-9428
VL - 22
SP - 19168
EP - 19178
JO - Journal of Materials Chemistry
JF - Journal of Materials Chemistry
IS - 36
ER -