Bifunctional Gold Nanoparticles Destroy Bacterial Pathogens with Antibiotic and Thermal Killing

A team of bioengineers has designed a novel class of targeted bifunctional nanoparticles that attacks pathogenic bacteria with both antibiotic and photo-activated thermal killing strokes.

Investigators at the University of Arkansas (Fayetteville, USA) were searching for alternative methods to treat infections caused by the "ESKAPE" group of pathogens (Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), which have developed antibiotic resistance and cause the majority of nosocomial infections.

Towards this end they developed a nanoparticle drug delivery system based on polydopamine-coated gold nanocages. These nanoparticles could be coated with an antibiotic and labeled with antibodies to guide them to specific bacterial targets. The gold particles could be induced to release the antibiotic while warming to a lethal temperature upon exposure to low levels of laser light.

The investigators used Staphylococcus aureus as a proof-of-principle ESKAPE pathogen to demonstrate that an appropriate antibiotic (daptomycin) could be incorporated into polydopamine-coated gold nanocages and that daptomycin-loaded gold nanocages could be conjugated to antibodies targeting a species-specific surface protein (staphylococcal protein A; Spa) as a means of achieving selective delivery of the nanoparticles directly to the bacterial cell surface.

They reported in the February 16, 2016, online edition of the journal ACS Infectious Diseases that targeting specificity was confirmed by demonstrating a lack of binding to mammalian cells, reduced photothermal and antibiotic killing of the Spa-negative species Staphylococcus epidermidis, and reduced killing of S. aureus in the presence of unconjugated anti-Spa antibodies. In addition, they demonstrated that laser irradiation at levels within the current safety standard for use in humans could be used to achieve both a lethal photothermal effect and controlled release of the antibiotic. The combination of antibiotic action and lethal heat eradicated all detectable S. aureus cells.

While the system was validated using free-floating bacterial cultures of both methicillin-sensitive and methicillin-resistant S. aureus strains, it was subsequently shown to be effective in the context of an established biofilm, thus indicating that this approach could be used to facilitate the effective treatment of intrinsically resistant biofilm infections.

“We believe that this approach could facilitate the effective treatment of infections caused by antibiotic-resistant bacteria, including those associated with bacterial biofilms, which are involved in a wide variety of bacterial infections,” said senior author Dr. Jingyi Chen, assistant professor of chemistry and biochemistry at the University of Arkansas.

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