title: Synthesis and Antibacterial Study of Sulfobetaine/Quaternary Ammonium-Modified Star-Shaped Poly[2-(dimethylamino)ethyl methacrylate]-Based Copolymers with an Inorganic Core.
abstract: Cationic polymethacrylates are interesting candidates for bacterial disinfectants since they can be made in large-scale by various well-established polymerization techniques such as atom transfer radical polymerization (ATRP). However, they are usually toxic or ineffective in serum and various strategies to improve their biocompatibility or nonfouling property have often resulted in compromised bactericidal activity. Also, star-shaped polymers are less explored than linear polymers for application as antibacterial compounds. In this paper, star polymers with poly[2-(dimethylamino)ethyl methacrylate] (PDMA) as the arms and polyhedral oligomeric silsesquioxane (POSS) as the core (POSS-g-PDMA) were successfully synthesized by ATRP. The minimum inhibition concentrations (MICs) of the synthesized POSS-g-PDMA are in the range of 10-20 μg/mL. POSS-g-PDMA was further modified by various hydrophilization strategies in attempting to reduce hemolysis. With quaternization of POSS-g-PDMA, the antibacterial activities of the obtained quaternary polymers are almost unchanged and the copolymers become relatively nonhemolytic. We also copolymerized sulfobetaine (SB) with POSS-g-PDMA to obtain random and block PDMA-co-PSB arm structures, where the PDMA and poly(sulfobetaine) were the cationic and zwitterionic blocks, respectively. The random cationic-zwitterionic POSS-g-(PDMA-r-PSB) copolymers showed poor antibacterial activity, while the block POSS-g-(PDMA-b-PSB) copolymers retained the antibacterial and hemolytic activity of the pristine POSS-g-PDMA. Further, the block copolymers of POSS-g-(PDMA-b-PSB) showed enhanced antifouling property and serum stability as seen by their nanoparticle size stability in the presence of serum and reduced red blood cell aggregation; the POSS-g-(PDMA-b-PSB) also somewhat retained its MIC in blood unlike the quaternized or random zwitterionic copolymers. The antibacterial kinetics study showed that Escherichia coli can be killed within 30 min by both random and block copolymers of POSS-g-(PDMA-co-PSB). Finally, our POSS star polymers showed low toxicity to zebrafish embryo and could be potentially used in aquaculture antibacterial applications.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Pu
authors.forename: Zheng
authors.initials: Z
authors.lastname: Hou
authors.forename: Mya Mya
authors.initials: MM
authors.lastname: Khin
authors.forename: Rubi
authors.initials: R
authors.lastname: Zamudio-Vázquez
authors.affiliation: Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research) , 61 Biopolis Drive, 138673, Singapore.
authors.forename: Kar Lai
authors.initials: KL
authors.lastname: Poon
authors.forename: Hongwei
authors.identifier: 0000-0003-2841-3344
authors.initials: H
authors.lastname: Duan
authors.forename: Mary B
authors.identifier: 0000-0003-3761-7517
authors.initials: MB
authors.lastname: Chan-Park
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001622:Betaine / Q000031:analogs & derivatives* / Q000737:chemistry; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008689:Methacrylates / Q000737:chemistry*; D051379:Mice; D008826:Microbial Sensitivity Tests; D041681:NIH 3T3 Cells; D011108:Polymers / Q000138:chemical synthesis* / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D015027:Zebrafish / Q000196:embryology
chemical_list: D000900:Anti-Bacterial Agents; D008689:Methacrylates; D011108:Polymers; D000644:Quaternary Ammonium Compounds; D001622:Betaine; C483727:sulfobetaine; C049840:2-(dimethylamino)ethyl methacrylate