Synergism of Water Shock and a Biocompatible Block Copolymer Potentiates the Antibacterial Activity of Graphene Oxide

Significance Statement

There is an urgent need to find alternative routes to control the spreading of antibiotics-resistant bacteria. Graphene and its water-soluble form graphene oxide (GO) were previously shown to be promising antibacterial agents. However, their antibacterial activity was relatively low and they show toxicity to human cells at high dose of usage. This study demonstrated a new strategy for significantly enhancing the antibacterial activity of graphene oxide. It showed that graphene oxide can kill 99% of bacteria when mixed with a human-friendly detergent in salt-reduced water. Further, the mixture of graphene oxide and Pluronic displays over 50% lower toxicity to human skin cells than the effect of graphene oxide alone. The developed strategy relies on the combination of two effects. The first effect is coming from the water itself. Bacteria inevitably undergo swelling when faced with salt-reduced water which puts a stress on bacterial envelope due to occurrence of microscopic damages. The second effect comes from pluronic; a bio-friendly polymer widely used in drug formulations and food applications. Pluronic increases the stability of graphene oxide in solution and also helps graphene oxide to interact with bacteria better by surrounding the bacterial cells more effectively. Water and detergents are undoubtedly the most common cleaning agents. This study may open the door for graphene oxide to be a widespread cleaning agent for fighting bacteria.

About the author

Yuan Chen received his BEng in Chemical Engineering and MEng in Biochemical Engineering from Tsinghua University. He obtained his PhD in Chemical Engineering at Yale University in 2005. He is currently a Professor at School of Chemical and Biomolecular Engineering (CBE), The University of Sydney. He joined the School of Chemical and Biomedical Engineering in Nanyang Technological University (NTU) in Singapore as an Assistant Professor in 2005. He was promoted to a tenured Associate Professor in 2010. He was visiting Associate Professor at Brown University in 2010 and visiting Chair Professor at Tianjin University of Technology in China 2011-2015. He served as Head of CBE Division in NTU from July 2011 to June 2014. He received an Excellence in Review Award from CARBON in 2015, a Young Scientist Award from the Singapore National Academy of Science in 2011, a Tan Chin Tuan Exchange Fellowship in Engineering in 2010, and JSPS exchange award in 2009. He is currently associate editor for Carbon (Elsevier), editorial board member for Nanomaterials, and Heliyon (Elsevier). His research focuses on developing scalable chemical processes to synthesize carbon nanomaterials with well-defined nanoscale structures, assembling nanoscale carbon nanomaterials into functional macroscale systems, and utilizing these novel materials for sustainable energy, environmental and biomedical applications.

About the author

Enis Karahan earned BSc double-degree in Chemical Engineering and Molecular Biology & Genetics from İstanbul Technical University. He received his MSc in Materials Science and Engineering at Koç University. Holding Singapore International Graduate Award (SINGA), he currently pursues his PhD studies in Bioengineering at Nanyang Technological University and Singapore Institute of Manufacturing Technologies of A*STAR. In addition to his academic experience, he also has an industrial background majorly gained in an R&D department of a textile company focused on polymer technologies. His expertise covers a broad spectrum of materials science including self-assembly of multilayered surface coatings, noncovalent functionalization of nanoparticles, and antibacterial, biomedical, and environmental applications of carbon-based nanocomposites to name a few. To date, he has over ten publications in peer-reviewed journals on his account.

Journal Reference

Small. 2016 Feb;12(7):951-62.

Karahan HE^1,2, Wei L¹, Goh K¹, Wiraja C¹, Liu Z¹, Xu C^1,3, Jiang R¹, Wei J², Chen Y^1,4.

[expand title=”Show Affiliations”]

School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637459, Singapore.
Singapore Institute of Manufacturing Technology (SIMTech), Singapore, 638075, Singapore.
NTU-Northwestern Institute of Nanomedicine, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.
School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, 2006, Australia.[/expand]

Abstract

Graphene oxide (GO) is promising in the fight against pathogenic bacteria. However, the antibacterial activity of pristine GO is relatively low and concern over human cytotoxicity further limits its potential. This study demonstrates a general approach to address both issues. The developed approach synergistically combines the water shock treatment (i.e., a sudden decrease in environmental salinity) and the use of a biocompatible block copolymer (Pluronic F-127) as a synergist co-agent. Hypoosmotic stress induced by water shock makes gram-negative pathogens more susceptible to GO. Pluronic forms highly stable nanoassemblies with GO (Pluronic-GO) that can populate around bacterial envelopes favoring the interactions between GO and bacteria. The antibacterial activity of GO at a low concentration (50 μg mL(-1) ) increases from <30% to virtually complete killing (>99%) when complemented with water shock and Pluronic (5 mg mL(-1) ) at ≈2-2.5 h of exposure. Results suggest that the enhanced dispersion of GO and the osmotic pressure generated on bacterial envelopes by polymers together potentiate GO. Pluronic also significantly suppresses the toxicity of GO toward human fibroblast cells. Fundamentally, the results highlight the crucial role of physicochemical milieu in the antibacterial activity of GO. The demonstrated strategy has potentials for daily-life bacterial disinfection applications, as hypotonic Pluronic-GO mixture is both safe and effective.

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