Abstract

The rising incidence of antibiotic-resistant infections from contaminated surfaces in hospitals or implanted medical devices has led to increasing interest in new antibacterial surfaces. Photoactivatable surfaces that can generate cytotoxic reactive oxygen species under exposure to ambient light is a promising approach to inactivation of surface-borne microorganisms. There is growing interest in the use of quantum dots (QDs) as light-harvesting agents for photobactericidal applications, but the cadmium in commonly used QDs will restrict clinical application. Herein, the photobactericidal activity of novel polyurethane substrates containing cadmium-free QDs was tested against clinical multidrug-resistant Gram-positive and Gram-negative bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA) and a carbapenemase-producing strain of Escherichia coli ( E. coli). To enhance the capacity for reactive oxygen species generation, QDs were incorporated into the polymer with a photosensitizing dye, crystal violet. Close proximity between the QD and dye enables electron and energy transfer processes leading to generation of cytotoxic singlet oxygen and superoxide radicals. A QD solution in cyclohexane was premixed with a solution of CV in the more polar solvent, dichloromethane, to promote the formation of QD-CV nanocomposite complexes via CV adsorption. This solution was then used to embed the QDs and crystal violet into medical grade polyurethane via swell-encapsulation. The combination of QD and CV elicited significant synergistic antibacterial activity under visible light against MRSA within 1 h (99.98% reduction) and E. coli within 4 h (99.96% reduction). Photoluminescence lifetime and singlet oxygen phosphorescence measurements demonstrated that interaction between the QDs and the crystal violet occurs within the polymer and leads to enhanced generation of reactive oxygen species. Strong inhibition of kill was observed using the superoxide scavenger, superoxide dismutase. The efficacy of these QD-CV polymer substrates, that can harvest light across the visible spectrum, against multidrug-resistant bacteria demonstrates the feasibility of this approach.

Highlights

  • Each year, over 4 million patients in the European Union and 2 million in the United States acquire a healthcare-associated infection (HAI), contributing to roughly 110 000 and 99 000 associated deaths, respectively.[1,2] HAIs which are referred to as nosocomial infections lead to prolonged suffering for patients and in many cases longer hospital stays

  • This molecular rotor effect is diminished when crystal violet (CV) is dissolved in high viscosity solvents or bound to proteins, and CV fluorescence from the first excited singlet state can be measured[44−46] Likewise, when CV is encapsulated in the polymer where the spatial constraint imposed by the matrix will restrict the rotor effect, the CV fluorescence is evident.[14,46]

  • We have shown that indium-based quantum dots (QDs) nanoparticles and CV can be embedded into polyurethane via the swell−encapsulation− shrink technique using a simple “one-pot” dipping process

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Summary

Introduction

Over 4 million patients in the European Union and 2 million in the United States acquire a healthcare-associated infection (HAI), contributing to roughly 110 000 and 99 000 associated deaths, respectively.[1,2] HAIs which are referred to as nosocomial infections lead to prolonged suffering for patients and in many cases longer hospital stays. The rising incidence of antimicrobial resistance (AMR) whereby bacteria become resistant to previously effective medications further exacerbates the impact of HAIs: more than 70% of the bacteria that causes HAIs are resistant to at least one commonly prescribed antibiotic.[3] Excessive and often unnecessary antibiotic use increases the selective pressure on bacterial populations, creating a pool of resistant genes some of which can transfer horizontally between populations and create multidrug-resistant (MDR) HAIs that are increasingly difficult. Received: January 31, 2019 Accepted: March 11, 2019 Published: March 11, 2019.

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