title: Broad-Spectrum Antimicrobial Star Polycarbonates Functionalized with Mannose for Targeting Bacteria Residing inside Immune Cells.
abstract: In this study, a series of star-shaped polycarbonates are synthesized by metal-free organocatalytic ring-opening polymerization of benzyl chloride (BnCl) and mannose-functionalized cyclic carbonate monomers (MTC-BnCl and MTC-ipman) with heptakis-(2,3-di-O-acetyl)-β-cyclodextrin (DA-β-CD) as macroinitiator. The distributions and compositions of pendent benzyl chloride and protected mannose group (ipman) units are facilely modulated by varying the polymerization sequence and feed ratio of the monomers, allowing precise control over the molecular composition, and the resulting polymers have narrow molecular weight distribution. After deprotection of ipman groups and quaternization with various N,N-dimethylalkylamines, these star polymers with optimized compositions of cationic and mannose groups in block and random forms exhibit strong bactericidal activity and low hemolysis. Furthermore, the optimal mannose-functionalized polymer demonstrates mannose receptor-mediated intracellular bactericidal activity against BCG mycobacteria without inducing cytotoxicity on mammalian cells at the effective dose. Taken together, the materials designed in this study have potential use as antimicrobial agents against diseases such as tuberculosis, which is caused by intracellular bacteria.
authors.affiliation: Institute of Bioengineeringand Nanotechnology (IBN), 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
authors.forename: Chuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: Institute of Bioengineeringand Nanotechnology (IBN), 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.|NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 117456, Singapore.
authors.forename: Sangeetha
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: Singapore Immunology Network, 8A Biomedical Grove, Immunos Building, 138648, Singapore.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Bioengineeringand Nanotechnology (IBN), 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
authors.forename: Shaoqiong
authors.initials: S
authors.lastname: Liu
authors.affiliation: Singapore Immunology Network, 8A Biomedical Grove, Immunos Building, 138648, Singapore.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Lu
authors.affiliation: IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Coady
authors.affiliation: Institute of Bioengineeringand Nanotechnology (IBN), 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
authors.forename: Wei
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Singapore Immunology Network, 8A Biomedical Grove, Immunos Building, 138648, Singapore.|University Hospital Basel, Basel, Switzerland.
authors.forename: Gennaro
authors.initials: G
authors.lastname: De Libero
authors.affiliation: Singapore Immunology Network, 8A Biomedical Grove, Immunos Building, 138648, Singapore.
authors.forename: Amit
authors.initials: A
authors.lastname: Singhal
authors.affiliation: IBM Almaden Research Center, 650 Harry Road, San Jose, CA, 95120, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Hedrick
authors.affiliation: Institute of Bioengineeringand Nanotechnology (IBN), 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
authors.forename: Yi Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000276:immunology* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D002412:Cations / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects / Q000276:immunology; D008322:Mammals / Q000276:immunology / Q000382:microbiology; D008358:Mannose / Q000737:chemistry*; D011076:Polycarboxylate Cement / Q000737:chemistry*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry; D047392:beta-Cyclodextrins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology
chemical_list: D000890:Anti-Infective Agents; D002412:Cations; D011076:Polycarboxylate Cement; D011108:Polymers; D047392:beta-Cyclodextrins; C005506:polycarbonate; D008358:Mannose
keywords: broad-spectrum antimicrobial activity; immune cell targeting; intracellular antibacterial effect; mannose; star polycarbonates