40 KJEMI 6 2025 Nesrine Bali Date: 17th of June PhD thesis: Polymer Coating Strategies for Tailored Iron Oxide Nanocomposites in Nanomedicine Trial lecture: Emulsion polymerization: synthetic and colloidal aspects Assessment Committee • First opponent: Dr hab. Fabienne Gauffre Rennes, Institute of Chemical Science, France • Second opponent: Dr. Wilhelm Glomm, SINTEF Industry, Norway • Chair of the committee: Associate Professor Solon Oikonomopoulos, Department of Chemistry, NTNU Supervisors • Main supervisor: Associate Professor Sulalit Bandyopadhyay, Department of Chemical Engineering, NTNU • Co-supervisor: Dr. Magnar Bjørås, Department of Clinical and Molecular Medicine, NTNU Summary of thesis Iron oxide nanoparticles (IONPs) have been used in a myriad of applications in the field of nanomedicine for both in vivo and in vitro settings, including in diagnostics, as imaging contrast agents, and in drug delivery carriers, owing to their superparamagnetic properties. Their efficacy mostly relies on their size, surface functionalization and magnetic strength. However, prolonged exposure to aqueous environments often leads to degradation processes that compromise their stability and performance. To tackle this challenge, IONPs are usually coated organic or inorganic coatings, although this can come at the expense of their magnetic properties. This thesis explored different strategies to synthesize iron oxide-based nanocomposites that can be used for diagnostics and drug delivery purposes, while maintaining their magnetic functionality in biologically relevant sizes. In situ polymerization and flash nanoprecipitation of preformed polymer were the two main strategies compared. First, the in situ polymerization of polyacrylic acid (PAA) was investigated in the presence of IONPs synthesized by co-precipitation, via a design of experiment (DoE) approach. The resulting nanocomposites were thoroughly characterized by dynamic light scattering (DLS), colorimetric carboxyl group quantification, thermogravimetric analysis (TGA), attenuated total reflection Fourier-transform infrared spectroscopy (ATR-FTIR), and vibrating sample magnetometry (VSM). The starting pH and use of high initiator concentration were shown to respectively influence polymerization kinetics and produce a mono-layer coverage of PAA that preserved the magnetic strength of IONPs and enhanced their colloidal stability. PAA-IONPs were then used to develop of a new cost-effective technology for nucleic acid extraction that performs on par with or better than commercial kits. Next, the thesis focused on the encapsulation of iron oxide nanoclusters (IONCs) synthesized by the polyol method, in poly(lactid-co-glycolic) acid (PLGA) nanoparticles via flash nanoprecipitation, a high-throughput continuous-flow mixing system. Synthesis parameters such as streams flow rates, type of organic solvent, addition of surfactant, polymer molecular weight and polymer:IONC ratio were systematically investigated, while PLGA NPs and PLGA-IONCs were characterized by DLS, VSM and transmission electron microscopy (TEM). This work provided insights into the nucleation and growth mechanisms of PLGA NPs under fast mixing conditions as described by the LaMer model and complemented by a diffusion-limited growth framework. Based on these results, a ternary composition diagram was established to identify the Ouzo region where monodisperse PLGA NPs formed spontaneously. Using a straight-forward and surfactant-free method, complete encapsulation of IONCs and formation of PLGA-IONC core-shell structures were demonstrated to strictly occur beyond the Ouzo domain at fast mixing conditions. This method enabled the streamlined and reproducible design of magneto-sensitive nanocarriers with strong magnetic properties, longterm stability (≥4 months), and high functionalization potential, making them well-suited for personalized nanomedicine and theranostics.
RkJQdWJsaXNoZXIy MTQ3Mzgy