title: Acid-Labile Poly(glycidyl methacrylate)-Based Star Gene Vectors.
abstract: It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.
authors.affiliation: ‡Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029 China.|§Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 China.
authors.forename: Yan-Yu
authors.initials: YY
authors.lastname: Yang
authors.affiliation: ‡Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029 China.|§Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Shen
authors.affiliation: ‡Key Laboratory of Carbon Fiber and Functional Polymers (Beijing University of Chemical Technology), Ministry of Education, Beijing 100029 China.|§Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029 China.
authors.forename: Fu-Jian
authors.initials: FJ
authors.lastname: Xu
authors.forename: De-Cheng
authors.initials: DC
authors.lastname: Wu
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010957:Plasmids; D011109:Polymethacrylic Acids / Q000737:chemistry* / Q000627:therapeutic use; D014162:Transfection
chemical_list: D001672:Biocompatible Materials; D011109:Polymethacrylic Acids; C042535:polyglycidyl methacrylate; D004247:DNA
keywords: acetal linker; acid-lability; biodegradation; gene vector; star-shaped