Enzyme-responsive nanoparticles: enhancing the ability of endolysins to eradicate Staphylococcus aureus biofilm.
Mariana Blanco MassaniDennis ToSusanne MeileMathias SchmelcherDavid GintsburgDébora C Coraça-HuberAnna SeyboldMartin J LoessnerAndreas Bernkop-SchnürchPublished in: Journal of materials chemistry. B (2024)
Stimuli-responsive nanomaterials show promise in eradicating Staphylococcus aureus biofilm from implants. Peptidoglycan hydrolases (PGHs) are cationic antimicrobials that can be bioengineered to improve the targeting of persisters and drug-resistant bacteria. However, these molecules can be degraded before reaching the target and/or present limited efficacy against biofilm. Therefore, there is an urgent need to improve their potency. Herein, PGH-polyphosphate nanoparticles (PGH-PP NPs) are formed by ionotropic gelation between cationic PGHs and anionic polyphosphate, with the aim of protecting PHGs and delivering them at the target site triggered by alkaline phosphatase (AP) from S. aureus biofilm. Optimized conditions for obtaining M23-PP NPs and GH15-PP NPs are presented. Size, zeta potential, and transmission electron microscopy imaging confirm the nanoscale size. The system demonstrates outstanding performance, as evidenced by a dramatic reduction in PGHs' minimum inhibitory concentration and minimum bactericidal concentration, together with protection against proteolytic effects, storage stability, and cytotoxicity towards the Caco-2 and HeLa cell lines. Time-kill experiments show the great potential of these negatively charged delivery systems in overcoming the staphylococcal biofilm barrier. Efficacy under conditions inhibiting AP proves the enzyme-triggered delivery of PGHs. The enzyme-responsive PGH-PP NPs significantly enhance the effectiveness of PGHs against bacteria residing in biofilm, offering a promising strategy for eradicating S. aureus biofilm.
Keyphrases
- staphylococcus aureus
- pseudomonas aeruginosa
- biofilm formation
- drug resistant
- candida albicans
- methicillin resistant staphylococcus aureus
- cancer therapy
- transcription factor
- multidrug resistant
- randomized controlled trial
- cystic fibrosis
- acinetobacter baumannii
- high resolution
- systematic review
- signaling pathway
- cell proliferation
- risk assessment
- oxide nanoparticles
- deep learning
- photodynamic therapy
- cell death
- atomic force microscopy
- bacillus subtilis
- high speed