Nanoparticles have been touted as wonder materials for a wide range of applications including as pharmaceutical agents, and specifically as an alternative to conventional small-molecule antibiotics. Unfortunately, they have proven inefficient in practical applications. However, bactericidal activity of metal-based nanoparticles is possible against multidrug-resistant bacteria isolated in the clinic but efficacy depends strongly on how well the particles binding to the microbes.
Writing in this journal, a German team explains how they have used a controllable nanoparticle model, to demonstrate how it is small nanoparticle size, rather than specific material or the charge on the particles that affects the formation of a nanoparticle-bacteria complex. However, their study also shows that the binding and so the antibiotic activity of a nanoparticle is reduced by the presence of biomolecule coronas, acquired in pathophysiological environments, such as wounds or blood, causing bacterial resistance. That said, a low pH environment can restore activity and overcome such resistance, the team reports. [Siemer, S. et al. Mater Today (2018); DOI: 10.1016/j.mattod.2018.10.041]
The team demonstrated these effects in two models with silver nanoparticles - the wax moth, Galleria mellonella, and mice. The low pH-induced complex formation which is critical to inhibition of Staphylococcus aureus skin wound infection was demonstrated. The resistance mechanism revealed in this study provides new insight into why nanoparticle "antibiotics" have not been as successful as the early hyperbole surrounding their development would have suggested. However, the study also offers a route from lower activity to greater efficacy that might well lead to new antibiotics based on metallic nanoparticles.
Fundamentally, the team showed that at acidic pH, the negative surface charge of the pathogen is lowered through protonation of surface molecules. This in turn increases the electrostatic interactions with the bacteria of the nanoparticles that are otherwise precluded access because they become coated with corona molecules.
The team points out that as well as topical, skin applications for antibiotic nanoformulations, there is also the potential to use them in the blood system, in wounds, and in chest infection, and also infection of the oro-gastrointestinal tract. The revelations about pH and activity made by the team could nudge nano-antibiotics forward in these areas at last. The team adds that their model based on the invertebrate G. mellonella could be used in early research prior to studies in mammals.