Probing the Coupled Equilibria between Metal Nanoparticles, Antibiotics and Components of the Extracellular Matrix in Biofilms with SERS

Understanding the interplay between nanoparticles, biomaterials and drug molecules in biological environments is important but studying these interactions in complex systems such as biofilms is challenging. Here, surface-enhanced Raman spectroscopy (SERS) with gold nanostars (NS) was used to monitor how biofilm components influence the binding and SERS signals of two antibiotics, levofloxacin (Levo) and ampicillin (Amp). The SERS signals of both antibiotics were reduced by approximately 70% (Levo) and 90% (Amp) in biofilm environments. Investigations of mixtures of model biofilm components: adenine (nucleic acids), alginate (polysaccharides) and albumin (proteins), revealed that their interactions with NS are governed by coupled equilibria. This gave surprising results, for example, alginate reduced the interference from adenine and albumin, so adding alginate increased the intensity of the antibiotic signals 4x. These findings highlight the importance of matrix component interactions in modulating detection sensitivity and show that these effects are critical in allowing clinically relevant detection levels to be achieved.