Laser-induced vapor nanobubbles: a new local hotspot in the anti-biofilm landscape?

One of the reasons for the increase in bacterial tolerance to antibiotics is the limited penetration of antibiotics through biofilms. Strategies that overcome the biofilm diffusion barrier by interfering with the dense biofilm architecture are highly sought after. In our study we demonstrated that laser-induced vapor nanobubbles (VNB) can locally disrupt biofilms and enhance the penetration and efficacy of antibiotics.

The promise of laser-induced VNB

Laser-induced VNB are a photothermal phenomenon in which sensitizing nanoparticles, such as plasmonic gold nanoparticles (AuNP), are irradiated with high-intensity short laser pulses, causing their temperature to increase by several hundreds of degrees. Consequently, the water surrounding the particles quickly evaporates within nanoseconds, resulting in the formation of VNB around the AuNP surface. The shockwaves created by quickly expanding and collapsing VNB hold the potential for disrupting biofilms and enhance the diffusion of antimicrobial agents deep into the biofilm [1,2].

In a first study we demonstrated that laser-induced VNB could locally disrupt the tightly packed sessile cells of both Gram-negative (Burkholderia multivorans, Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) biofilms. This enhanced the diffusion and hence efficacy of subsequently applied tobramycin between 10- to 3000-fold, depending on the organism and treatment condition [3].

Encouraged by these promising results, we next investigated the potential of VNB to disrupt wound-associated biofilms, which is a clinical condition that could be compatible with laser treatment. In particular, we investigated if laser-induced VNB can increase the efficacy of a broad range of commercially available antimicrobials frequently used in wound care, including povidone-iodine, chlorhexidine, benzalkonium chloride, cetrimonium bromide and mupirocin. We found an enhanced effect for certain combinations of antimicrobials and bacterial biofilms, such as benzalkonium chloride (~ 21x) in P. aeruginosa biofilms, and cetrimonium bromide (~ 24x) and mupirocin (~ 53x) in S. aureus biofilms. The latter result could even be enhanced to a complete loss of survival when VNB-formation was repeated a couple of times. For other combinations, however, no beneficial effect of VNB was found, which hinted to the fact that in those cases the diffusion barrier did not play a role. This hypothesis was found to be valid, as similar results were found when these antimicrobials were added to biofilms that were completely disrupted by vortexing and ultrasound. This led to the conclusion that VNB can indeed enhance the efficacy of those antimicrobials that experience a diffusion barrier in biofilms.

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