Haiqing Yin, Han Chang Kang, Kang Moo Huh, You Han Bae
{"title":"Biocompatible, pH-sensitive AB(2) Miktoarm Polymer-Based Polymersomes: Preparation, Characterization, and Acidic pH-Activated Nanostructural Transformation.","authors":"Haiqing Yin, Han Chang Kang, Kang Moo Huh, You Han Bae","doi":"10.1039/C2JM33750A","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":16297,"journal":{"name":"Journal of Materials Chemistry","volume":"22 36","pages":"91968-19178"},"PeriodicalIF":0.0000,"publicationDate":"2012-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C2JM33750A","citationCount":"50","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Materials Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1039/C2JM33750A","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 50
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.