title: pH and hydrogen peroxide dual responsive supramolecular prodrug system for controlled release of bioactive molecules.
abstract: Nowadays, cancer is one of the most fatal threatens to human health. By utilizing the differences of cell environment between cancer cells and their normal counterparts as assembly-disassembly triggers, various smart drug nanocarriers have been designed to fight the cancer. Nevertheless, most of them are still not robust enough. One important reason is that they merely focus on a single stimulus. Thus, in order to achieve a better therapeutic effect, constructing multi responsive polymers is of great significance. However, most of multi responsive polymers used, up until now, are mainly based on block polymers synthesized via traditional polymerization methods, which are relatively time-consuming and laborious. Here in this article, a facile strategy preparing smart polymers with dual responsiveness (endosomal pH and over produced H2O2) was proposed and realized by orthogonal assembly of β-CD-hydrazone-DOX and PEG-Fc. The obtained polymers were found to be able to spontaneously assemble into micelles in water, indicating their potential applications as drug nanocarriers. In vitro study revealed that the release of the encapsulated DOX was significantly enhanced by both H2O2 and low pH at 5.0. Furthermore, fluorescence microscopy and flow cytometry analysis showed that the assembled supramolecular prodrug micelles could be internalized into cancer cells. These properties suggested their promising application in cancer therapy.
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China.
authors.forename: Yangjun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China.
authors.forename: Xiangsheng
authors.initials: X
authors.lastname: Liu
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China. Electronic address: jinqiao@zju.edu.cn.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Jin
authors.affiliation: MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, Zhejiang, China. Electronic address: jijian@zju.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Ji
mesh_terms: D001672:Biocompatible Materials / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000494:pharmacology; D005296:Ferrous Compounds / Q000737:chemistry; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000737:chemistry; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008027:Light; D000075163:Metallocenes; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D011092:Polyethylene Glycols / Q000737:chemistry; D011355:Prodrugs / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D012542:Scattering, Radiation; D013056:Spectrophotometry, Ultraviolet; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D005296:Ferrous Compounds; D006835:Hydrazones; D000075163:Metallocenes; D008823:Micelles; D011355:Prodrugs; D047392:beta-Cyclodextrins; D011092:Polyethylene Glycols; D004317:Doxorubicin; D006861:Hydrogen Peroxide; C031215:betadex; C004998:ferrocene
keywords: Dual responsive; Host–guest interactions; Prodrug micelles; β-Cyclodextrin