Development of biofilm-specific magnetic iron oxide nanoparticles carrying 2-aminoimidazole biofilm inhibitors

Over the years, multifunctional nanomaterials and in particular nanoparticles have been investigated thoroughly for their use in many applications, including catalysis, imaging, energy-based research and biomedical applications. Especially iron oxide nanoparticles are extensively used in hyperthermia treatment, medical imaging, cancer therapy and drug delivery thanks to their biocompatibility, chemical stability, low toxicity and superparamagnetic behavior. In this dissertation the development of multifunctional superparamagnetic iron oxide nanoparticles is presented, which act as a magnetic carrier for in-house developed 5-aryl-2-amino-imidazole biofilm inhibitors to increase the practical applicability of biofilm inhibitors. In the first part of this work, the synthesis and the possibility to control the size and magnetization of iron oxide nanoparticles in a forced hydrolysis synthesis method is described. Tuning the size of the nanoparticle by varying the surfactant/precursor ratio is a frequently used method and can be applied in various synthetic methods. This knowledge was used to determine the ideal nanoparticle size and applied in the thermal decomposition method, which was used in the following chapters due to the very good shape control, large scalability and the ability to produce high quality nanoparticles with very narrow size distribution. In the second part of this research, a new ligand is designed and synthesized to connect in-house developed 5-Ar-2-AI-based biofilm inhibitors to the nanoparticle. Evaluation of the developed bioconjugated nanoparticles is tested against a broad panel of bacterial species, including Salmonella Typhimurium, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Since the substitution pattern of 5-Ar-2-AIs determines their activity and toxicity, N1-substituted, 2N-substituted as well as N1-2N-disubstituted 5-Ar-2-AIs are evaluated. The effect of magnetic forces on the biofilm inhibition is analyzed in the final part of this dissertation. An alternating magnetic field is applied after incubation to determine the effect of magnetic nanoparticle heating. Furthermore, the nanoparticles are enriched at the surface by applying magnetic forces underneath a biofilm prior to incubation.

Jaar van publicatie:2019

Toegankelijkheid:Embargoed