Potent antibacterial nanoparticles for pathogenic bacteria.

Antibiotic-resistant bacteria have emerged because of the prevalent use of antibacterial agents. Thus, new antibacterial agents and therapeutics that can treat bacterial infections are necessary. Vancomycin is a potent antibiotic. Unfortunately, some bacterial strains have developed their resistance toward vancomycin. Nevertheless, it has been demonstrated that vancomycin-immobilized nanoparticles (NPs) are capable to be used in inhibition of the cell growth of vancomycin-resistant bacterial strains through multivalent interactions. However, multistep syntheses are usually necessary to generate vancomycin-immobilized NPs. Thus, maintaining the antibiotic activity of vancomycin when the drug is immobilized on the surface of NPs is challenging. In this study, a facile approach to generate vancomycin immobilized gold (Van-Au) NPs through one-pot stirring of vancomycin with aqueous tetrachloroauric acid at pH 12 and 25 °C for 24 h was demonstrated. Van-Au NPs (8.4 ± 1.3 nm in size) were readily generated. The generated Van-Au NPs maintained their antibiotic activities and inhibited the cell growth of pathogens, which included Gram-positive and Gram-negative bacteria as well as antibiotic-resistant bacterial strains. Furthermore, the minimum inhibitory concentration of the Van-Au NPs against bacteria was lower than that of free-form vancomycin. Staphylococcus aureus-infected macrophages were used as the model samples to examine the antibacterial activity of the Van-Au NPs. Macrophages have the tendency to engulf Van-Au NPs through endocytosis. The results showed that the cell growth of S. aureus in the macrophages was effectively inhibited, suggesting the potential of using the generated Van-Au NPs as antibacterial agents for bacterial infectious diseases.

[1]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[2]  Michael J. MacCoss,et al.  Aminoglycoside antibiotics induce bacterial biofilm formation , 2005, Nature.

[3]  D. Granger,et al.  Macrophage production of nitrogen oxides in host defence against microorganisms. , 1991, Research in immunology.

[4]  Tsai-Jung Yu,et al.  photothermal agents for targeted hyperthermia of nosocomial and antibiotic-resistant bacteria , 2011 .

[5]  D. Geng,et al.  pH induced size-selected synthesis of PtRu nanoparticles, their characterization and electrocatalytic properties , 2007 .

[6]  Juncheng Liu,et al.  Facile "green" synthesis, characterization, and catalytic function of beta-D-glucose-stabilized Au nanocrystals. , 2006, Chemistry.

[7]  Yu-Chie Chen,et al.  Multifunctional Fe₃O₄/alumina core/shell MNPs as photothermal agents for targeted hyperthermia of nosocomial and antibiotic-resistant bacteria. , 2011, Nanomedicine.

[8]  Vikas Berry,et al.  Self-assembly of nanoparticles on live bacterium: an avenue to fabricate electronic devices. , 2005, Angewandte Chemie.

[9]  A. Shiratsuchi,et al.  Strategy against Host Innate Immunity in Macrophages : A Novel Bacterial aureus Staphylococcus TLR 2-Mediated Survival of Yoshinobu , 2007 .

[10]  A. Shiratsuchi,et al.  TLR2-Mediated Survival of Staphylococcus aureus in Macrophages: A Novel Bacterial Strategy against Host Innate Immunity1 , 2007, The Journal of Immunology.

[11]  Thommey P. Thomas,et al.  Dendrimer-based multivalent vancomycin nanoplatform for targeting the drug-resistant bacterial surface. , 2013, ACS nano.

[12]  C. Perry,et al.  Antibiotic mediated synthesis of gold nanoparticles with potent antimicrobial activity and their application in antimicrobial coatings , 2010 .

[13]  Hao Wang,et al.  Vancomycin-modified mesoporous silica nanoparticles for selective recognition and killing of pathogenic gram-positive bacteria over macrophage-like cells. , 2013, ACS applied materials & interfaces.

[14]  Bing Xu,et al.  Using biofunctional magnetic nanoparticles to capture vancomycin-resistant enterococci and other gram-positive bacteria at ultralow concentration. , 2003, Journal of the American Chemical Society.

[15]  Yu-Chie Chen,et al.  Dextran-encapsulated photoluminescent gold nanoclusters: synthesis and application , 2014, Journal of Nanoparticle Research.

[16]  Z. Shervani,et al.  Carbohydrate-directed synthesis of silver and gold nanoparticles: effect of the structure of carbohydrates and reducing agents on the size and morphology of the composites. , 2011, Carbohydrate research.

[17]  Stefan Weigand,et al.  Antibacterial natural products in medicinal chemistry--exodus or revival? , 2006, Angewandte Chemie.

[18]  Yu-Chie Chen,et al.  Affinity capture using vancomycin-bound magnetic nanoparticles for the MALDI-MS analysis of bacteria. , 2005, Analytical chemistry.

[19]  D. Levine,et al.  Vancomycin: a history. , 2006, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[20]  D. Cardo,et al.  Estimating Health Care-Associated Infections and Deaths in U.S. Hospitals, 2002 , 2007, Public health reports.

[21]  B. Simard,et al.  Vancomycin architecture dependence on the capture efficiency of antibody-modified microbeads by magnetic nanoparticles. , 2007, Chemical communications.

[22]  M. Arnold,et al.  Hydrodynamic characterization of surfactant encapsulated carbon nanotubes using an analytical ultracentrifuge. , 2008, ACS nano.

[23]  Bing Xu,et al.  Presenting Vancomycin on Nanoparticles to Enhance Antimicrobial Activities , 2003 .

[24]  J. Greenspan,et al.  Pediatric Vancomycin Use in 421 Hospitals in the United States, 2008 , 2012, PloS one.

[25]  S. Ricke,et al.  Vancomycin-resistant enterococci from nosocomial, community, and animal sources in the United States , 1996, Antimicrobial agents and chemotherapy.

[26]  Yu-Chie Chen,et al.  Multifunctional Fe3O4@Au nanoeggs as photothermal agents for selective killing of nosocomial and antibiotic-resistant bacteria. , 2009, Small.

[27]  Zhengrong Cui,et al.  Physical Characterization and Macrophage Cell Uptake of Mannan-Coated Nanoparticles , 2003, Drug development and industrial pharmacy.

[28]  Dong-Hwang Chen,et al.  Vancomycin-modified LaB6@SiO2/Fe3O4 composite nanoparticles for near-infrared photothermal ablation of bacteria. , 2013, Acta biomaterialia.

[29]  Shannon Ryan,et al.  Vancomycin-modified nanoparticles for efficient targeting and preconcentration of Gram-positive and Gram-negative bacteria. , 2008, ACS nano.

[30]  Yu-Chie Chen,et al.  Functional Fe3O4/TiO2 core/shell magnetic nanoparticles as photokilling agents for pathogenic bacteria. , 2008, Small.

[31]  Ben Wong,et al.  Silver nanoparticles and polymeric medical devices: a new approach to prevention of infection? , 2004, The Journal of antimicrobial chemotherapy.

[32]  Stefan Weigand,et al.  Antibacterial Natural Products in Medicinal Chemistry — Exodus or Revival? , 2006 .

[33]  Chenjie Xu,et al.  Controlled PEGylation of Monodisperse Fe3O4 Nanoparticles for Reduced Non‐Specific Uptake by Macrophage Cells , 2007 .

[34]  Jianchao Sun,et al.  Ag nanoparticles and vancomycin comodified layered double hydroxides for simultaneous capture and disinfection of bacteria. , 2013, Journal of materials chemistry. B.

[35]  Vikas Berry,et al.  Deposition of CTAB-terminated nanorods on bacteria to form highly conducting hybrid systems. , 2005, Journal of the American Chemical Society.

[36]  A. Zahr,et al.  Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol). , 2006, Langmuir : the ACS journal of surfaces and colloids.

[37]  C. Perry,et al.  Facile one-pot synthesis of amoxicillin-coated gold nanoparticles and their antimicrobial activity , 2014, Gold Bulletin.

[38]  Yu-Chie Chen,et al.  Functional gold nanoparticles as photothermal agents for selective-killing of pathogenic bacteria. , 2007, Nanomedicine.