Iron oxide nanoparticles for antibacterial treatment: Self-assembled, thermoresponsive and multifunctional drug delivery

Research output: Book/anthology/dissertation/reportPh.D. thesisResearch

Biomaterial associated inflections pose an increasing social health problem, influenced by an aging world population, increased antimicrobial resistance and limited treatment options due to the biofilm mode of growth. Novel treatment options focus on tackling the biofilm specific challenges through the use of nanoparticles. Utilizing the intrinsic antibacterial, magnetic and externally induced hyperthermia properties of iron oxide nanoparticles (IONPs), the creation of a S. aureus biofilm specific, multi-functional thermoresponsive drug delivery system was envisioned.

Increasing the understanding of human S. aureus biofilm infections, the interactions between host and pathogen was investigated, displaying a high influence of the human extracellular matrix proteins fibrin, elastin and collagen. An improved in vitro biofilm model was created by optimization of ion concentrations and host interactions, providing a clinically relevant model for initial tests of novel therapeutics. Human extracellular matrix targeting nanobodies were expressed from literature or developed by llama immunization, intended for further structural understanding of interactions between bacteria and host proteins.

A novel IONP thermoresponsive drug delivery system was created based on 15 nm thermal decomposition IONP cores and a lipid micelle coating. The coating method allowed transformation of the IONPs from organic to aqueous solution, providing a completely monodisperse and long-term stable particle solution. Incorporating the amphiphilic model drug, R18, the thermoresponsive drug delivery properties was verified, displaying a receptor and temperature dependent release, with thermal release properties controlled by the lipid phase transition temperature. The particles displayed concentration and treatment dependent externally induced bulk hyperthermia upon magnetic or NIR induction, capable of inducing temperature controlled R18 release.

Creation of two different IONP liposome systems was attempted, incorporating the IONPs in either the liposome lumen or lipid bilayer for IONP controlled thermoresponsive drug delivery of hydrophilic drugs. IONP lumen incorporation appeared feasible and controllable, while IONP lipid bilayer incorporation was found highly troublesome, requiring stringent control of the self-assembly procedure. Neither liposome system could be developed into a final functional setup, and the thermoresponsive drug delivery properties was never verified.

Future project development entail verification of biofilm specific use and effect of the IONP drug delivery systems, incorporating actual drugs and attaching S. aureus biofilm specific targeting ligands, providing a novel multifunctional biofilm specific treatment option.
Original languageEnglish
Publication statusPublished - Feb 2020

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