Graphene oxide as an efficient antimicrobial nanomaterial for eradicating multi-drug resistant bacteria in vitro and in vivo.

Graphene is a novel two-dimensional nanomaterial with a growing number of practical applications across numerous fields. In this work, we explored potential biomedical applications of graphene oxide (GO) by systematically studying antibacterial capacity of GO in both macrophages and animal models. Three types of bacteria, including Klebsiella pneumoniae (Kp), Escherichia coli (E. coli) and P. aeruginosa (Pa) were used for in vitro study. Kp was also selected as a representative multidrug resistant (MDR) bacterium for in vivo study. In in vitro study, GO effectively eradicated Kp in agar dishes and thus protected alveolar macrophages (AM) from Kp infection in the culture. In the in vivo evaluation, GO were introduced intranasally into mouse lungs followed by testing organ tissue damage including lung, liver, spleen, and kidneys, polymorphonuclear neutrophil (PMN) penetration, bacterial dissemination, and mortality in Kp-infected mice. We found that GO can prohibit the growth and spread of Kp both in vitro and in vivo, resulting in significantly increased cell survival rate, less tissue injury, subdued inflammatory response, and prolonged mice survival. These findings indicate that GO could be a promising biomaterial for effectively controlling MDR pathogens.

[1]  Omid Akhavan,et al.  Toxicity of graphene and graphene oxide nanowalls against bacteria. , 2010, ACS nano.

[2]  Kai Yang,et al.  Tumor vasculature targeting and imaging in living mice with reduced graphene oxide. , 2013, Biomaterials.

[3]  Min Wu,et al.  Escherichia coli FPG and human OGG1 reduce DNA damage and cytotoxicity by BCNU in human lung cells. , 2002, American journal of physiology. Lung cellular and molecular physiology.

[4]  Z. Rao,et al.  Human 8-oxoguanine DNA glycosylase increases resistance to hyperoxic cytotoxicity in lung epithelial cells and involvement with altered MAPK activity , 2005, Cell Death and Differentiation.

[5]  S. Godet,et al.  Synthesis and antibacterial activity of silver nanoparticles against gram-positive and gram-negative bacteria. , 2012, Nanomedicine : nanotechnology, biology, and medicine.

[6]  Xiaodan Zhu,et al.  Killing dental pathogens using antibacterial graphene oxide. , 2015, ACS applied materials & interfaces.

[7]  A. Bansal,et al.  8-Oxoguanine-DNA glycosylase 1 deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice. , 2012, Free radical biology & medicine.

[8]  Hui Jiang,et al.  Gold nanoclusters and graphene nanocomposites for drug delivery and imaging of cancer cells. , 2011, Angewandte Chemie.

[9]  G. Gherardi,et al.  Potential novel therapeutic strategies in cystic fibrosis: antimicrobial and anti-biofilm activity of natural and designed α-helical peptides against Staphylococcus aureus, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia , 2012, BMC Microbiology.

[10]  H. Pei,et al.  Nanomaterial‐Based Fluorescent DNA Analysis: A Comparative Study of the Quenching Effects of Graphene Oxide, Carbon Nanotubes, and Gold Nanoparticles , 2013 .

[11]  M. Kelley,et al.  Expression of yeast apurinic/apyrimidinic endonuclease (APN1) protects lung epithelial cells from bleomycin toxicity. , 2001, American journal of respiratory cell and molecular biology.

[12]  J. Zhao,et al.  Fabrication of highly fluorescent graphene quantum dots using L-glutamic acid for in vitro/in vivo imaging and sensing. , 2013, Journal of materials chemistry. C.

[13]  Jing Kong,et al.  Lateral dimension-dependent antibacterial activity of graphene oxide sheets. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[14]  Yong-Chien Ling,et al.  Graphene-based photothermal agent for rapid and effective killing of bacteria. , 2013, ACS nano.

[15]  Rongqin Huang,et al.  Multifunctional mesoporous silica-coated graphene nanosheet used for chemo-photothermal synergistic targeted therapy of glioma. , 2013, Journal of the American Chemical Society.

[16]  Ping Wu,et al.  Fluorescence quenching of graphene oxide integrating with the site-specific cleavage of the endonuclease for sensitive and selective microRNA detection. , 2013, Analytical chemistry.

[17]  Heyou Han,et al.  Graphene oxide exhibits broad-spectrum antimicrobial activity against bacterial phytopathogens and fungal conidia by intertwining and membrane perturbation. , 2014, Nanoscale.

[18]  Canhua Huang,et al.  Lyn regulates inflammatory responses in Klebsiella pneumoniae infection via the p38/NF‐κB pathway , 2014, European journal of immunology.

[19]  Binjie Zhang,et al.  Autophagy plays an essential role in the clearance of Pseudomonas aeruginosa by alveolar macrophages , 2012, Journal of Cell Science.

[20]  Chunhai Fan,et al.  Graphene-based antibacterial paper. , 2010, ACS nano.

[21]  H. Ceri,et al.  ntibiotic resistance of mixed biofilms in cystic fibrosis : impact of emerging icroorganisms on treatment of infection usana , 2012 .

[22]  R. Ruoff,et al.  The chemistry of graphene oxide. , 2010, Chemical Society reviews.

[23]  A. Bansal,et al.  Caveolin‐1 plays a critical role in host immunity against Klebsiella pneumoniae by regulating STAT5 and Akt activity , 2012, European journal of immunology.

[24]  Milan Kolar,et al.  Silver colloid nanoparticles: synthesis, characterization, and their antibacterial activity. , 2006, The journal of physical chemistry. B.

[25]  Jing Kong,et al.  Antibacterial activity of graphite, graphite oxide, graphene oxide, and reduced graphene oxide: membrane and oxidative stress. , 2011, ACS nano.

[26]  Z. Marković,et al.  Photodynamic antibacterial effect of graphene quantum dots. , 2014, Biomaterials.

[27]  K. Novoselov,et al.  A roadmap for graphene , 2012, Nature.

[28]  Pedro J J Alvarez,et al.  Negligible particle-specific antibacterial activity of silver nanoparticles. , 2012, Nano letters.

[29]  Lin Li,et al.  The application of graphene oxide in drug delivery , 2012, Expert opinion on drug delivery.

[30]  Seong-Cheol Park,et al.  A helix-PXXP-helix peptide with antibacterial activity without cytotoxicity against MDRPA-infected mice. , 2014, Biomaterials.

[31]  Liangzhu Feng,et al.  Graphene in biomedicine: opportunities and challenges. , 2011, Nanomedicine.

[32]  A. Domb,et al.  Antibacterial activity of dental composites containing quaternary ammonium polyethylenimine nanoparticles against Streptococcus mutans. , 2006, Biomaterials.

[33]  R. Advíncula,et al.  On the antibacterial mechanism of graphene oxide (GO) Langmuir-Blodgett films. , 2015, Chemical communications.

[34]  Li Wei,et al.  Bacterial physiology is a key modulator of the antibacterial activity of graphene oxide. , 2016, Nanoscale.

[35]  P. Cochat,et al.  Et al , 2008, Archives de pediatrie : organe officiel de la Societe francaise de pediatrie.

[36]  Matthias Epple,et al.  Silver as antibacterial agent: ion, nanoparticle, and metal. , 2013, Angewandte Chemie.

[37]  H. Abdelhamid,et al.  Near infrared (NIR) laser mediated surface activation of graphene oxide nanoflakes for efficient antibacterial, antifungal and wound healing treatment. , 2015, Colloids and surfaces. B, Biointerfaces.

[38]  Mark Voorneveld,et al.  Preparation , 2018, Games Econ. Behav..

[39]  Z. Tong,et al.  Tailor-made Au@Ag core–shell nanoparticle 2D arrays on protein-coated graphene oxide with assembly enhanced antibacterial activity , 2013, Nanotechnology.

[40]  Haiping Fang,et al.  Destructive extraction of phospholipids from Escherichia coli membranes by graphene nanosheets. , 2013, Nature nanotechnology.

[41]  Zhouyi Guo,et al.  Synergistic effect of chemo-photothermal therapy using PEGylated graphene oxide. , 2011, Biomaterials.

[42]  W. Shao,et al.  Preparation, characterization, and antibacterial activity of silver nanoparticle-decorated graphene oxide nanocomposite. , 2015, ACS applied materials & interfaces.

[43]  Kai Yang,et al.  Nano-Graphene in Biomedicine: Theranostic Applications , 2013 .