Fructose-Enhanced Efficacy of Magnetic Nanoparticles against Antibiotic Resistant Biofilms
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Fructose-Enhanced Efficacy of Magnetic Nanoparticles against Antibiotic Resistant Biofilms N. Gozde Durmus1, Erik N. Taylor1 and Thomas J. Webster1,2 1 2
School of Engineering, Brown University, Providence, RI, USA 02912 Department of Chemical Engineering, Northeastern University, Boston, MA, USA 02215
ABSTRACT The emergence of methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections (HAI). HAI affect approximately 1.7 million patients each year in the U.S., resulting in up to 100,000 excess deaths, which leads to an estimated cost of more than $35 billion per year. Hence, there is an urgent clinical need to develop new therapies to reduce infections, without resorting to the use of antibiotics for which bacteria are developing a resistance towards. In this study, we designed superparamagnetic iron-oxide nanoparticles (SPION) to treat antibiotic-resistant biofilms and showed that SPION efficacy increases when they are used in combination with fructose. INTRODUCTION Biofilms are defined as communities of microorganisms that are adhered to a biotic or abiotic surface.[1, 2] These are complex heterogeneous communities embedded in an extracellular polymeric substance (EPS) matrix, which is composed of polysaccharides, nucleic acids, proteins and lipids.[3, 4] Biofilms are a major source of HAI due to their persistent growth on medical devices and surfaces. The surfaces of invasive medical devices serve as substrates for bacterial attachment, growth and biofilm formation.[5] Biofilm-forming bacteria can withstand host immune responses and become much less susceptible to antibiotics than their individual planktonic counterparts.[2, 6, 7] This causes the antibiotic resistance problem in the clinical settings. Therefore, there is a need to develop novel alternative antibacterial strategies. Superparamagnetic iron oxide particles (SPION) have been recently used in various biomedical applications for magnetic imaging, bioseperation and biodetection. They are also used for targeted drug delivery applications due to their magnetic properties.[8] Moreover, SPION have shown promising antibacterial properties.[9-12] Moreover, it has been shown that metabolic microenvironment is crucial for antibacterial applications.[13] In this study, our aim was to develop SPION to treat antibiotic-resistant biofilms and to increase SPION efficacy by using metabolic stimulation (i.e., using magnetic nanoparticles in combination with fructose). EXPERIMENTAL DETAILS Superparamagnetic iron oxide nanoparticles (SPION) were synthesized using a high temperature synthesis method in triethylene glycol (TREG) and capped with 4 mmol dimercaptosuccinic acid (DMSA). Particle size was analyzed by dynamic light scattering (DLS) measurements. For DLS analysis, SPION were diluted 1:1000 in double deionized water after
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they were sterile filtered by a 0.2 μm filter. A Zetasizer Nano ZS was used and five readings were taken for each sample. For bacteria experiments, an antibiotic-resistant strain (MRSA) (ATCC #70
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