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Abstract In a healthcare setting, biofilms are a major source of infection and difficult to eradicate once formed. Nanoparticles (NPs) can be designed to effectively penetrate biofilms to more efficiently either deliver antibiotic drugs throughout the biofilm matrix or elicit inherent antibiofilm activity. Antibacterial cerium oxide (CeO2) NPs were employed as core material and coated with a mesoporous silica shell (MSN) to generate cerium oxide coated mesoporous silica NPs (CeO2@MSN). Detailed studies of NP‐biofilm interactions are required to rationally develop NP platforms to prevent biofilm‐related infections. This work developed and implemented a unique label‐free analysis platform for the real‐time monitoring of bacterial biofilm formation and then assessed the interactions of antibacterial NPs. An analysis platform which allows bacterial biofilms to grow and develop in situ in flow within the multi‐parametric surface plasmon resonance (MP‐SPR) instrument was established. This enabled simultaneous monitoring and detection of biofilm growth phases, structure, and interactions between differentially charged CeO2@MSNs and bacterial biofilms. Positively charged antibacterial NPs (polyethyleneimine functionalized CeO2@MSNs) were found to be the most efficient to penetrate the biofilm. The MP‐SPR analysis platform was shown to be a powerful tool for monitoring biofilm development in real‐time and to analyze biofilm properties and NP‐biofilm interactions.

Stephanie Fulaz,1,* Henry Devlin,1,* Stefania Vitale,1 Laura Quinn,1 James P O’Gara,2 Eoin Casey1 1UCD School of Chemical and Bioprocess Engineering, University College Dublin, Dublin, Ireland; 2Department of Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland*These authors contributed equally to this workCorrespondence: Eoin CaseyUCD School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Dublin, IrelandEmail eoin.casey@ucd.ieBackground: Considering the timeline required for the development of novel antimicrobial drugs, increased attention should be given to repurposing old drugs and improving antimicrobial efficacy, particularly for chronic infections associated with biofilms. Methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are common causes of biofilm-associated infections but produce different biofilm matrices. MSSA biofilm cells are typically embedded in an extracellular polysaccharide matrix, whereas MRSA biofilms comprise predominantly of surface proteins and extracellular DNA (eDNA). Nanoparticles (NPs) have the potential to enhance the delivery of antimicrobial agents into biofilms. However, the mechanisms which influence the interactions between NPs and the biofilm matrix are not yet fully understood.Methods: To investigate the influence of NPs surface chemistry on vancomycin (VAN) encapsulation and NP entrapment in MRSA and MSSA biofilms, mesoporous silica nanoparticles (MSNs) with different surface functionalization (bare-B, amine-D, carboxyl-C, aromatic-A) were synthesised using an adapted Stöber method. The antibacterial efficacy of VAN-loaded MSNs was assessed against MRSA and MSSA biofilms.Results: The two negatively charged MSNs (MSN-B and MSN-C) showed a higher VAN loading in comparison to the positively charged MSNs (MSN-D and MSN-A). Cellular binding with MSN suspensions (0.25 mg mL− 1) correlated with the reduced viability of both MSSA and MRSA biofilm cells. This allowed the administration of low MSNs concentrations while maintaining a high local concentration of the antibiotic surrounding the bacterial cells.Conclusion: Our data suggest that by tailoring the surface functionalization of MSNs, enhanced bacterial cell targeting can be achieved, leading to a novel treatment strategy for biofilm infections.Keywords: Staphylococcus aureus, mesoporous silica nanoparticles, EPS matrix, antimicrobial, vancomycin, nanoparticle-biofilm interactions

In a healthcare setting, biofilms are a major source of infection and difficult to eradicate once formed. Nanoparticles (NPs) can be designed to effectively penetrate biofilms to more efficiently either deliver antibiotic drugs throughout the biofilm matrix or elicit inherent antibiofilm activity. Antibacterial cerium oxide (CeO 2 ) NPs were employed as core material and coated with a mesoporous silica shell (MSN) to generate cerium oxide coated mesoporous silica NPs (CeO 2 @MSN). Detailed studies of NP-biofilm interactions are required to rationally develop NP platforms to prevent biofilm-related infections. This work developed and implemented a unique label-free analysis platform for the real-time monitoring of bacterial biofilm formation and then assessed the interactions of antibacterial NPs. An analysis platform which allows bacterial biofilms to grow and develop in situ in flow within the multi-parametric surface plasmon resonance (MP-SPR) instrument was established. This enabled simultaneous monitoring and detection of biofilm growth phases, structure, and interactions between differentially charged CeO 2 @MSNs and bacterial biofilms. Positively charged antibacterial NPs (polyethyleneimine functionalized CeO 2 @MSNs) were found to be the most efficient to penetrate the biofilm. The MP-SPR analysis platform was shown to be a powerful tool for monitoring biofilm development in real-time and to analyze biofilm properties and NP-biofilm interactions., Competing Interests: Hongbo Zhang is an executive editor for Smart Medicine and was not involved in the editorial review or the decision to publish this article. All authors declare that there are no competing interests., (© 2023 The Authors. Smart Medicine published by Wiley-VCH GmbH on behalf of Wenzhou Institute, University of Chinese Academy of Sciences.)

Bacteria are essential components of all natural and many engineered systems. The most active fractions of bacteria are now recognized to occur as ‘biofilms’, where cells are attached and surrounded by a secreted matrix of sticky extracellular polymeric substances (EPS). Recent investigations have established that significant accumulation of nanoparticles (NPs) occurs in aquatic biofilms. These studies point to the emerging roles of biofilms for influencing partitioning and possibly transformations of NPs in both natural and engineered systems. While attached biofilms are efficient sponges for NPs, efforts to elucidate the fundamental mechanisms guiding interactions between NPs and biofilms have just begun. In this mini review, special attention is focused on NP-biofilm interactions within the aquatic environment. We highlight key physical, chemical and biological processes that affect interactions and accumulation of NPs by bacterial biofilms. We posit that these biofilm processes present the likely possibility for unique biological and chemical transformations of NPs. Ultimately, the environmental fate of NPs is influenced by biofilms, and therefore requires a more-in depth understanding of their fundamental properties.

Bacteria are essential components of all natural and many engineered systems. The most active fractions of bacteria are now recognized to occur as biofilms, where cells are attached and surrounded by a secreted matrix of "sticky" extracellular polymeric substances. Recent investigations have established that significant accumulation of nanoparticles (NPs) occurs in aquatic biofilms. These studies point to the emerging roles of biofilms for influencing partitioning and possibly transformations of NPs in both natural and engineered systems. While attached biofilms are efficient "sponges" for NPs, efforts to elucidate the fundamental mechanisms guiding interactions between NPs and biofilms have just begun. In this mini review, special attention is focused on NP-biofilm interactions within the aquatic environment. We highlight key physical, chemical, and biological processes that affect interactions and accumulation of NPs by bacterial biofilms. We posit that these biofilm processes present the likely possibility for unique biological and chemical transformations of NPs. Ultimately, the environmental fate of NPs is influenced by biofilms, and therefore requires a more in-depth understanding of their fundamental properties.