title: Synthesis of amphiphilic copolymers containing zwitterionic sulfobetaine as pH and redox responsive drug carriers.
abstract: Amphiphilic poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate)-r-poly(N-(3-sulfopropyl)-N-methacrylate-N,N-diethylammonium-betaine) (PCL-SS-PDEASB) was designed and synthesized successfully. pH and redox dually responsive micelles were prepared based on the obtained copolymers, with zwitterionic sulfobetaines as hydrophilic shell, DEA as pH sensitive content and disulfide as redox responsive linkage. The micelle diameters were all less than 200 nm and the micelle diameter distributions were narrow. These micelles could be triggered by pH and redox condition. The drug release from the drug-loaded micelles displayed fastest under simultaneously acidic and reductive conditions. Results of in vitro cell toxicity evaluation showed that introduction of sulfobetaines could greatly decrease the toxicity of poly(ɛ-caprolactone)-SS-poly(N,N-diethylaminoethyl methacrylate) (PCL-SS-PDEA) micelles. DOX-loaded PCL-SS-PDEASB micelles showed higher efficiency to kill HeLa cells than DOX-loaded PCL-PDEASB micelles. Half inhibitory concentration (IC50) of DOX-loaded PCL-SS-PDEASB micelles decreased with the content of sulfobetaines increasing and was even closer to that of DOX·HCl. Thus, the pH and redox dually responsive biodegradable micelles generated by PCL-SS-PDEASB may be potential smart drug carriers for tumor targeted delivery.
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Mengtan
authors.initials: M
authors.lastname: Cai
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Mengtian
authors.initials: M
authors.lastname: Leng
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Aijing
authors.initials: A
authors.lastname: Lu
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Liu
authors.initials: L
authors.lastname: He
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Xiaoxiong
authors.initials: X
authors.lastname: Xie
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Huang
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Yuhao
authors.initials: Y
authors.lastname: Ma
authors.affiliation: National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Chen
authors.affiliation: College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China; State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, People's Republic of China. Electronic address: luoxl_scu@126.com.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Luo
mesh_terms: D000818:Animals; D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008823:Micelles; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship; D013499:Surface Properties; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011108:Polymers; D013501:Surface-Active Agents; D001622:Betaine; D004317:Doxorubicin; C483727:sulfobetaine
keywords: Biodegradable micelles; Controlled release; Dual-response; Stimuli-sensitive; Sulfobetaine