Self-immolative polymers with potent and selective antibacterial activity by hydrophilic side chain grafting

We report the first example of a self-immolative polymer that exerts potent antibacterial activity combined with relatively low hemolytic toxicity. In particular, self-immolative poly(benzyl ether)s bearing pendant cationic ammonium groups and grafted poly(ethylene glycol) chains in their side chain...

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Bibliographic Details
Published in:Journal of materials chemistry. B, Materials for biology and medicine Materials for biology and medicine, 2018-11, Vol.6 (44), p.7217-7229
Main Authors: Ergene, Cansu, Palermo, Edmund F
Format: Article
Language:English
Subjects:
Ammonium
Antibacterial activity
Bactericidal activity
Cations
Composition
Copolymers
Cysteamine
Depolymerization
Fluorides
Grafting
Organic chemistry
Polyethylene glycol
Polymerization
Polymers
Selectivity
Toxicity
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Summary:We report the first example of a self-immolative polymer that exerts potent antibacterial activity combined with relatively low hemolytic toxicity. In particular, self-immolative poly(benzyl ether)s bearing pendant cationic ammonium groups and grafted poly(ethylene glycol) chains in their side chains were prepared via post-polymerization thiol-ene chemistry. These functional polymers undergo sensitive and specific triggered depolymerization into small molecules upon exposure to a designed stimulus (in this example, fluoride ions cleave a silyl ether end cap). The molar composition of the resulting statistical copolymers varied from 0 to 100% PEG side chains. The average molar mass of the pendant PEG chains was either 800 or 2000 g mol . The antibacterial and hemolytic activities were evaluated as a function of copolymer composition. Strong bactericidal activity (low μg mL MBC) was retained in the copolymers containing 25-50% PEG-800, whereas hemolytic toxicity monotonically decreased (up to HC >1000 μg mL ) with increasing PEG content. PEG-2000 was far less effective; both the MBC and HC decreased to a comparable extent with increasing PEGylation. Overall, the best cell type selectivity index (HC /MBC ∼ 28) was obtained for the copolymer containing ∼50% cysteamine and ∼50% PEG-800 side chains, as compared to the cationic homopolymer (HC /MBC < 1). Thus, the systematic tuning of the PEG graft density and chain length effectively enhances the cell-type selectivity of these self-immolative polymers by orders of magnitude.
ISSN:2050-750X
2050-7518
DOI:10.1039/c8tb01632a