Bacterial infections have become a global issue that requires urgent attention,particularly regarding to emergence of multidrug resistant bacteria.We developed quaternary amine-containing antimicrobial poly(bile acid)...Bacterial infections have become a global issue that requires urgent attention,particularly regarding to emergence of multidrug resistant bacteria.We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain.Interestingly,by choosing appropriate monomers,these cationic polymers can form core-shell micelles.These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species.It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities.Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers.展开更多
Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to...Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation,including local facial amphiphilicity and global amphiphilicity.This work conceptualizes Facial Amphiphilicity Index(FAI)as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy.FAI is a ratio of numbers of charges to rings,representing both compositions of hydrophilicity and hydrophobicity.Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria.Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs.Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid.While low and high FAIs respectively lead to higher and lower antimicrobial efficacy,in consideration of cytotoxicity,the sweet spot is typically suited with intermediate FAIs for each specific system.This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes.The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.展开更多
Compared with single-network hydrogels,double-network hydrogels offer higher mechanical strength and toughness.Integrating useful functions into double-network hydrogels can expand the portfolios of the hydrogels.We r...Compared with single-network hydrogels,double-network hydrogels offer higher mechanical strength and toughness.Integrating useful functions into double-network hydrogels can expand the portfolios of the hydrogels.We report the preparation of double-network metallopolymer hydrogels with remarkable hydration,antifouling,and antimicrobial properties.These cationic hydrogels are composed of a first network of cationic cobaltocenium polyelectrolytes and a second network of polyacrylamide,all prepared via radical polymerization.Antibiotics were further installed into the hydrogels via ion-complexation with metal cations.These hydrogels exhibited significantly enhanced hydration,compared with polyacrylamide-based hydrogels,while featuring robust mechanical strength.Cationic metallopolymer hydrogels exhibited strong antifouling against oppositely charged proteins.These antibiotic-loaded hydrogels demonstrated a synergistic effect on the inhibition of bacterial growth and antifouling of bacteria,as a result of the unique ion complexation of cobaltocenium cations.展开更多
基金The authors would like to thank National Science Foundation(DMR-1608151).
文摘Bacterial infections have become a global issue that requires urgent attention,particularly regarding to emergence of multidrug resistant bacteria.We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain.Interestingly,by choosing appropriate monomers,these cationic polymers can form core-shell micelles.These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species.It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities.Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers.
文摘Facial amphiphilicity is an extraordinary chemical structure feature of a variety of antimicrobial peptides and polymers.Vast efforts have been dedicated to small molecular,macromolecular and dendrimer-like systems to mimic this highly preferred structure or conformation,including local facial amphiphilicity and global amphiphilicity.This work conceptualizes Facial Amphiphilicity Index(FAI)as a numerical value to quantitatively characterize the measure of chemical compositions and structural features in dictating antimicrobial efficacy.FAI is a ratio of numbers of charges to rings,representing both compositions of hydrophilicity and hydrophobicity.Cationic derivatives of multicyclic compounds were evaluated as model systems for testing antimicrobial selectivity against Gram-negative and Gram-positive bacteria.Both monocyclic and bicyclic compounds are non-antimicrobial regardless of FAIs.Antimicrobial efficacy was observed with systems having larger cross-sectional areas including tricyclic abietic acid and tetracyclic bile acid.While low and high FAIs respectively lead to higher and lower antimicrobial efficacy,in consideration of cytotoxicity,the sweet spot is typically suited with intermediate FAIs for each specific system.This can be well explained by the synergistic hydrophobic-hydrophobic and electrostatic interactions with bacterial cell membranes and the difference between bacterial and mammalian cell membranes.The adoption of FAI would pave a new avenue toward the design of next-generation antimicrobial macromolecules and peptides.
基金The study was supported by the National Institutes of Health(No.R01AI120987).
文摘Compared with single-network hydrogels,double-network hydrogels offer higher mechanical strength and toughness.Integrating useful functions into double-network hydrogels can expand the portfolios of the hydrogels.We report the preparation of double-network metallopolymer hydrogels with remarkable hydration,antifouling,and antimicrobial properties.These cationic hydrogels are composed of a first network of cationic cobaltocenium polyelectrolytes and a second network of polyacrylamide,all prepared via radical polymerization.Antibiotics were further installed into the hydrogels via ion-complexation with metal cations.These hydrogels exhibited significantly enhanced hydration,compared with polyacrylamide-based hydrogels,while featuring robust mechanical strength.Cationic metallopolymer hydrogels exhibited strong antifouling against oppositely charged proteins.These antibiotic-loaded hydrogels demonstrated a synergistic effect on the inhibition of bacterial growth and antifouling of bacteria,as a result of the unique ion complexation of cobaltocenium cations.
