Light-activated nanodrug could thwart antibiotic resistance

John Murphy, MDLinx | April 01, 2016

Researchers have demonstrated a novel photoactive nanodrug that could defeat antibiotic-resistant infections. They put an antibiotic inside a protective gold nanocage; when exposed to laser light, the cage releases the drug directly on the bacterial surface, according to a study published online in the journal ACS Infectious Diseases.

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Photoactive nanodrug thwarts  photoactive nanodrug that could defeat antibiotic-resistant infections

This photoactive nanodrug is composed of an antibiotic encased in a protective gold nanocage. When exposed to laser light, the cage releases the drug directly on the surface of the pathogen. (Image: University of Arkansas for Medical Sciences)

“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 study co-author Jingyi Chen, PhD, Assistant Professor in the Department of Chemistry and Biochemistry in the J. William Fulbright College of Arts and Sciences at University of Arkansas, in Fayetteville, AR.

Several years ago, infectious disease specialists identified 6 important pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) as the “ESKAPE bugs” because they continue to escape the lethal action of antibiotics.

In this proof-of-principle study, the researchers chose Staphylococcus aureus as their target ESKAPE bug to test their novel approach. Then they selected an appropriate antibiotic, daptomycin, and encased it into nanoconstructs, which are nanoscale cages made of gold that are coated with polydopamine. Next, they attached certain antibodies to the nanoconstructs; these antibodies target a specific staphylococcal surface protein to selectively send the nanoconstructs directly to the bacterial cell surface.

Once the nanoconstructs reached their target, the researchers exposed them to laser light (at levels within the current safety standard for use in humans), which the gold nanocages converted to heat. The resultant photothermal effect “melted” the nanocages and released the antibiotic from the polydopamine coating directly onto the pathogen.

The researchers validated the therapeutic effects of this approach using planktonic bacterial cultures of both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant (MRSA) strains. They subsequently showed the nanodrug method to be effective even against an intrinsically resistant biofilm.

“The even better news is that the technology we developed would be readily adaptable to other bacterial pathogens that cause such infections, including the other ESKAPE pathogens,” said co-author Mark Smeltzer, PhD, Professor in the Department of Microbiology and Immunology at University of Arkansas for Medical Sciences and director of the Center for Microbial Pathogenesis and Host Inflammatory Responses, in Little Rock, AR.

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