Vancomycin-decorated microbubbles as a theranostic agent for Staphylococcus aureus biofilms

Vancomycin-decorated microbubbles as a theranostic agent for Staphylococcus aureus biofilms

Kouijzer, Joop J.P. (Erasmus Medical Center)
Lattwein, Kirby R. (Erasmus Medical Center)
Beekers, Inés (Erasmus Medical Center)
Langeveld, Simone A.G. (Erasmus Medical Center)
Leon-Grooters, Mariël (Erasmus Medical Center)
Strub, Jean Marc (University of Strasbourg)
Oliva, Estefania (University of Strasbourg)
de Jong, N. (TU Delft ImPhys/Medical Imaging; Erasmus Medical Center)
van der Steen, A.F.W. (TU Delft ImPhys/Medical Imaging; Erasmus Medical Center)

2021

Bacterial biofilms are a huge burden on our healthcare systems worldwide. The lack of specificity in diagnostic and treatment possibilities result in difficult-to-treat and persistent infections. The aim of this in vitro study was to investigate if microbubbles targeted specifically to bacteria in biofilms could be used both for diagnosis as well for sonobactericide treatment and demonstrate their theranostic potential for biofilm infection management. The antibiotic vancomycin was chemically coupled to the lipid shell of microbubbles and validated using mass spectrometry and high-axial resolution 4Pi confocal microscopy. Theranostic proof-of-principle was investigated by demonstrating the specific binding of vancomycin-decorated microbubbles (vMB) to statically and flow grown Staphylococcus aureus (S. aureus) biofilms under increasing shear stress flow conditions (0–12 dyn/cm²), as well as confirmation of microbubble oscillation and biofilm disruption upon ultrasound exposure (2 MHz, 250 kPa, and 5,000 or 10,000 cycles) during flow shear stress of 5 dyn/cm² using time-lapse confocal microscopy combined with the Brandaris 128 ultra-high-speed camera. Vancomycin was successfully incorporated into the microbubble lipid shell. vMB bound significantly more often than control microbubbles to biofilms, also in the presence of free vancomycin (up to 1000 µg/mL) and remained bound under increasing shear stress flow conditions (up to 12 dyn/cm²). Upon ultrasound insonification biofilm area was reduced of up to 28%, as confirmed by confocal microscopy. Our results confirm the successful production of vMB and support their potential as a new theranostic tool for S. aureus biofilm infections by allowing for specific bacterial detection and biofilm disruption.

Biofilm
Sonobactericide
Targeted microbubble
Theranostic
Ultrasound
Vancomycin

http://resolver.tudelft.nl/uuid:3b7c4bad-cefd-4d6c-9f4f-0e7f765e942c

https://doi.org/10.1016/j.ijpharm.2021.121154

0378-5173

International Journal of Pharmaceutics, 609

Institutional Repository

journal article

© 2021 Joop J.P. Kouijzer, Kirby R. Lattwein, Inés Beekers, Simone A.G. Langeveld, Mariël Leon-Grooters, Jean Marc Strub, Estefania Oliva, N. de Jong, A.F.W. van der Steen, More Authors